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Purpose: The aim of this study was to assess the effects three electrospun fiber membranes on postoperative adhesion formation in rat surgical models., Materials and Methods: The PEG-PHBV (polyethylene glycol and poly-β-hydroxybutyrate valerate), PLA(Polylactic acid) and CS-PEG(chitosan and polyethylene glycol) were used for submicrometric membranes fabrication by electrospinning. A total of 64 SD male rats were randomly divided into 4 groups, one control group and 3 treatment groups, each consisting of 16 rats. The rats were underwent median laparotomy and standardized abrasion of the cecum. The indicated membranes were applied intraperitoneally at the end of the surgical procedure in the treatment groups, while the controls left without treatment. Two and four weeks after surgery respectively, a relaparotomy was made for adhesion grading and histopathological examination, Hydroxyproline (Hyp) levels at the adhesion sites in each group were measured., Results: The electrospun submicrometric membranes significantly reduced not only the incidence of adhesion but also the adhesion grading scales (p < 0.05 compared to the control group) at both two weeks and four weeks after the initial operation. Furthermore, the fibrosis grades were also higher in control groups as compared with the submicrometric membrane groups. Hyp levels in the control group was significant higher than the three experiment groups at both 2 and 4 weeks time points (p < 0.05). There were no statistical differences between the different treatment groups at either time points., Conclusions: Three electrospun submicrometric membranes were soft, flexible, easy to handle, and effectively reduced adhesion formation in rat modes.

Flexible and protease resistant (G4S) n linkers are used extensively in protein engineering to connect various protein domains. Recently, several groups have observed xylose-based O-glycosylation at linker Ser residues that yield unwanted heterogeneity and may affect product quality. Because of this, an engineering effort was implemented to explore different linker sequence constructs. Here, we demonstrate the presence of an unexpected hydroxylation of a prolyl residue in the linker, made possible through the use of high-resolution mass spectrometry (HR-MS) and MS n . The discovery started with the detection of a poorly resolved ∼+17 Da mass addition at the reduced protein chain level of an Fc-fusion construct by liquid chromatography-MS. Upon further investigation at the peptide level using HR-MS, the mass increase was determined to be +15.99 Da and was localized to the linker peptide SLSLSPGGGGGPAR [210-223]. This peptide corresponds to the C-terminus of Fc [210-216], the G4P linker [217-221], and first 2 amino acids of a growth factor [222-223]. The linker peptide was first subjected to MS 2 with collision-induced dissociation (CID) activation. The fragmentation profile localized the modification to the GGGPA [218-222] portion of the peptide. Accurate mass measurement indicated that the modification is an addition of an oxygen and cannot be CH 4 , thus eliminating several possibilities such as Pro→Leu. However, other possibilities cannot be ruled out. Higher-energy collision-induced dissociation (HCD)-MS 2 and MS 3 using CID/CID were both unable to differentiate between Ala222→ Ser222 or Pro221→ Hyp221. Finally, MS 3 using high-resolution CID/HCD confirmed the mass increase to be a Pro221→Hyp221 post-translational modification.

Background: Although several studies suggested hypoxia as an important microenvironmental factor contributing to inflammation and fibrosis in chronic liver diseases, the mechanism of this process is not fully understood. We considered hypoxia inducible factor (HIF-1α) as a key transcription factor in liver fibrosis. The aim of the study was to evaluate the mechanisms of signaling pathway during bile duct ligation (BDL)-induced liver fibrosis in rats., Methods: BDL animal model of liver fibrosis was used in the study. Male Wistar rats were divided randomly into two experimental groups: sham group (n = 15), BDL group (n = 30). Hydroxyproline (Hyp) content as a marker of collagen accumulation in liver of rats subjected to BDL was evaluated according to the method described by Gerling B et al. Expression of signaling proteins [integrin β 1 receptor, HIF-1α, nuclear factor kappa B (NF-κB), and transforming growth factor (TGF-β)] was evaluated applying Western-immunoblot analysis. In all experiments, the mean values for six assays ± standard deviations (SD) were calculated. The results were submitted to the statistical analysis using the Student's "t" test, accepting p < 0.05 as significant., Results: Ligation of bile ducts was found to increase Hyp content in rat liver, accompanied by increase of HIF-1α expression during 10 weeks after BDL. The Hyp level was time dependent. There was not such a difference in control group (p < 0.001). Simultaneously expression of NF-κB, TGF-β, β 1 -integrin receptor was significantly elevated starting from sixth week after ligation. Activity of metalloproteinases 2 and 9 in the livers were increased 1 week after surgery and remained increased until the end of the experiment., Conclusions: The mechanism of development of liver fibrosis involves activation of Matrix metalloproteinase-2 (MMP-2) and Matrix metalloproteinase-9 (MMP-9), upregulation of HIF-1α transcriptional activity and its related factors, NF-κB and TGF-β. It suggests that they may represent targets for the treatment of the disease.

Context: The quantification of total collagen is of major importance in a wide range of research areas, including the study of cutaneous wound healing and new drugs trials., Objective: The total collagen content in skin biopsies was compared by biochemical hydroxyproline assay and by two computer-aided histomorphometric analyses of histological sections., Materials and Methods: Two methods were used to evaluate collagen formation: the hydroxyproline assay, as the gold standard and histomorphometric image analysis of the filled areas by corresponding stained collagen fibres, using picrosirius and Gomori's trichrome staining. The image analyses were determined by digital densitometry recognition using computer-aided ImageJ software. One-way ANOVA, simple linear regression and ANCOVA were applied for the statistical analysis and correlation., Results: In a simple linear regression analysis carried out on the 14th day period after the induction of skin injury, three techniques, picrosirius red (F = 33.57, p = 0.00), Gomori's trichrome (F = 81.61, p = 0.00) and hydroxyproline content (F = 16.85, p = 0.00) were able to detect collagen production. After scale adjustment, there were no significant differences among either the slopes (F = 1.17, p = 0.32) or the intercepts (F = 0.69, p = 0.51) of the estimated regression lines. It seems that a highly significant correlation exists between the histomorphometrical analysis and hydroxyproline assay., Discussion and Conclusion: The morphometric analysis proved to be adequate and can be used as a simple, rapid, low-cost technology for evaluating total collagen in cutaneous wound specimens, compared with the gold standard hydroxyproline assay.

Aim: The purpose of this study was to evaluate the effects of hyperbaric oxygen (HBO) and HBO preconditioning (pre-HBO) on experimental wound healing and tensile strength in the colonic anastomosis of rats., Materials and Methods: A total of 21 Sprague-Dawley rats were divided into three random groups of equal numbers: sham operation, pre-HBO, and HBO. Sham group was given standard left colon resection and end-to-end anastomosis; pre-HBO group received HBO as one dose + colonic resection + anastomosis; HBO group was given colonic resection + anastomosis + HBO. HBO was administrated at 24-hr intervals and relaparatomy was performed on the fifth day. Malondialdehyde (MDA), myeloperoxidase (MPO), superoxide dismutase (SOD), glutathione peroxidase (GSH-Px), interleukin (IL)-10, IL-6, tumor necrosis factor-alpha (TNF-α), and hydroxy (OH)-proline levels and anastomotic burst pressure were evaluated., Results: Burst pressure and OH-proline levels markedly increased in the HBO group compared with the sham and pre-HBO groups. When compared with the sham group, MDA and MPO levels were significantly decreased in the HBO and pre-HBO groups. In contrast to these findings, SOD and GSH-Px levels were increased in the HBO group as compared with the sham and pre-HBO groups. TNF-α, IL-6, and IL-10 values were detected at low levels in the HBO group as compared with other groups., Conclusions: HBO administration accelerated wound healing and strengthened the anastomotic tissue. In the light of these results, the HBO administration has beneficial effects and contributed to wound healing in colonic anastomosis. But, as expected, pre-HBO did not alter the results significantly.

Background: Several researchers have investigated how wound healing is effected by supplementation with each of the following amino acids : arginine (Arg), glutamine (Glu), and beta-hydroxy beta-methylbutyrate (HMB). This research investigates how a combination of these amino acids improves the wound healing associated with anastomoses., Methods: We tested the effects of a combination of Arg, Glu, and HMB on the healing of colon anastomoses in 50 male rats. We randomly divided the animals into two equal groups. In each animal, the cecum was transected from its midpoint to create an end-to end anastomosis. During the first postoperative week, Group 1 (G1) animals were fed standard chow, and Group 2 (G2) animals were fed standard chow plus a ready-to-use supplement that contained a mixture of Arg, Glu, and HMB. At the end of the week, all of the rats were sacrificed, and a cecum segment containing the anastomosis line was resected. Bursting pressure and tissue hydroxyproline were measured for all animals., Results: The mean values for hydroxyproline were 0.0013 ng/mg protein/ml (SD +/-0.00075) and 0.034 ng/mg protein/ ml (SD +/- 0.022) for G1 and G2, respectively (p <0.0001). The mean values for bursting pressure measurements were 122.8 mmHg (SD +/- 9.4) and 192.8 mmHg (SD+/- 31) for G1 and G2, respectively (p <0.0001). Statistically significant differences between the groups in terms of both bursting pressure levels and tissue hydroxyproline levels were observed., Conclusion: In an animal model of colon surgery, supplementation with a combination of three amino acids seemingly benefits anastomosis healing.

Purpose: We aimed to investigate whether caffeic acid phenethyl ester (CAPE) prevents detrimental systemic effects of intestinal ischemia-reperfusion (IR) injury on colonic anastomotic wound healing., Methods: This experimental study was conducted on 48 male Wistar albino rats. The rats were randomly allocated into four groups and a left colonic anastomosis was performed in all rats: (i) sham-operated group (n = 12), laparatomy without intestinal IR injury; (ii) sham + CAPE group (n = 12), identical to Group 1 except for CAPE treatment (10 μmol/kg, intravenously); (iii) intestinal IR group (n = 12), 60 min of superior mesenteric ischemia followed by reperfusion; and (iv) IR + CAPE-treated group (n = 12) (10 μmol/kg, intravenously, 30 min before the construction of colonic anastomosis). On the postoperative day 7, the rats were subjected to relaparotomy for in vivo measurement of the colonic anastomotic bursting pressure. A colonic segment including the anastomotic site was resected for histopathological evaluation and biochemical analyses. The plasma proinflammatory cytokine levels were measured. Body weight changes were examined., Results: CAPE treatment significantly increased colonic anastomotic bursting pressures, and colonic anastomotic tissue hydroxyproline contents and antioxidant parameters (p < .05), and significantly decreased oxidative stress markers in colonic anastomotic tissues and plasma proinflammatory cytokine levels (p < .05). Histopathological scores were significantly better due to CAPE administration (p < .05)., Conclusions: This study clearly showed that CAPE treatment prevented the delaying effects of remote IR injury on colonic anastomotic wound healing. Further clinical studies are required to determine whether CAPE has a useful role in the enhancement of gastrointestinal anastomotic wound healing during particular surgeries in which IR-induced organ injury occurs.

China's government has prohibited the addition of simply hydrolyzed animal protein from solid leather waste into milk. The objective of this study was to produce a monoclonal antibody against L-hydroxyproline, a special amino acid in hydrolyzed animal protein. L-hydroxyproline was derivatized with N-acetylsulfanilyl chloride and 5-chlorovaleric acid to synthesize the haptens HP1 and HP2. Then, two immunogens from the two haptens were prepared to produce the antibodies. Results showed that only HP1 was able to stimulate the animal immune system and generate the specific antibody to L-hydroxyproline (as the formation of HP1). The obtained monoclonal antibody from HP1 and the heterologous coating hapten HP2 were incorporated into a competitive indirect enzyme linked immunosorbent assay (ELISA) to determine the antibody's specificity and sensitivity. The IC(50) and the limit of detection for HP1 were 0.16 μg/mL and 0.05 μg/mL respectively. The antibody showed low crossreactivity to parental L-hydroxyproline and showed negligible crossreactivity to D-hydroxyproline and other amino acids. The monoclonal antibody was therefore suitable for the development of an immunoassay to monitor the simply hydrolyzed animal protein from solid leather waste in foodstuffs with L-hydroxyproline as the target analyte.

Purpose: The objective of the present study was to assess the effects of oriental sweet gum (Liquidambar orientalis Mill.) storax on partial-thickness and full-thickness wounds compared to conventional wound dressings in a porcine model., Methods: Six young Yorkshire pigs were used. Sixteen square excisional wounds measuring 3 × 3 cm were performed per animal. The wounds were allocated to one of the four treatment modalities: storax, hydrocolloid dressing, silver sulfadiazine, and control groups. Partial-thickness wounds were created in two pigs, and tissue samples were harvested on days 4 and 8, respectively. Full-thickness wounds were created in four pigs, and tissue samples were taken on days 4, 8, 14, and 21, respectively. Histologically, all wounds were examined for re-epithelialization and granulation tissue formation. Tissue hydroxyproline content and wound contraction areas were measured., Results: In storax-applied group, there was a greater depth of granulation tissue at 4 and 8 days compared to all other groups (p < .0125), and there was a faster re-epithelialization at 21 days compared to both hydrocolloid dressing and control groups in full-thickness wounds (p < .0125). Tissue hydroxyproline content and wound contraction did not differ significantly between the groups., Conclusion: The results of this study indicate that topical application of storax enhanced both re-epithelialization and granulation tissue formation in full-thickness wounds. Further studies are indicated in this important area of wound healing research to evaluate the clinical efficacy of this storax and search for the mechanisms that explain its effects.

Introduction: 2-octyl-cyanoacrylate may be a good alternative in ischemic colon anastomosis without impairment of tissue perfusion., Methods: Forty male Wistar albino rats were randomized into four experimental groups (n = 10 in each group). In group 1 (control), a well-perfused left colonic segment was transected, and free ends were anastomosed by propylene sutures. In groups 2, 3, and 4, the animals underwent a standardized surgical procedure to induce ischemic left colon anastomosis. In group 2, an end-to-end anastomosis was created using six interrupted 6-0 polypropylene sutures between ischemic edges. In group 3, after approximating the mesenteric and antimesenteric edges of the anastomosis with two 6-0 polypropylene sutures, 2-octyl-cyanoacrylate was applied between the edges. In group 4, anastomosis was created by the same technique as described in group 2, and additionally 2-octyl-cyanoacrylate was applied on suture line. Rats were killed on day 4 following operation. Anastomotic integrity, intraperitoneal adhesion scores, anastomotic bursting pressures, and tissue hydroxyproline levels were recorded. Histopathological examination of the anastomosis was also performed., Results: There were no statistically significant differences among groups with respect to anastomotic integrity (p =.142). The mean bursting pressure values were 81.1 +/- 23.83, 43.3 +/- 26.06, 15.8 +/- 11.3, and 17.6 +/- 18.02 in groups 1, 2, 3, and 4, respectively. There were no statistically significant differences among groups 2, 3, and 4 with respect to tissue hydroxyproline levels and bursting pressure levels. The highest adhesion scores were observed in groups 3 and 4., Discussion: 2-octyl cyanoacrylate does not have additional advantages in the healing of experimental ischemic colon anastomosis.

Objectives: In dentine, erosive lesion progression and efficacy of fluoridation measures for symptomatic therapy of dental erosion are both dependent on the presence of the organic matrix. In patients with eating disorders in combination with chronic vomiting, the demineralized organic matrix can be degraded by gastric enzymes. The aim of this study was to investigate the effect of pepsin on erosion progression and the efficacy of fluoride in dentine., Material and Methods: Human dentine specimens were prepared and randomly divided into 4 groups of 20 specimens each. They were subjected to a cyclic de- and remineralization procedure for 9 days. For demineralization (6 x 2 min per day), an HCl solution (pH 1.6) was used in all groups. In two groups, pepsin (1.5 mg mL(-1)) was added to the demineralization solution. Fluoridation was performed in two groups 6 x 1 min per day with a mouth rinse (Olaflur/SnF(2); 250 ppm F(-)) after demineralization with both the HCl solution and the pepsin containing solution. Degradation of collagen was quantified by analyzing hydroxyproline and tissue loss was determined microradiographically. SEM images were taken in addition., Results: In the pepsin group, 1.72 (0.26) microg mL(-1) (mean (SD)) hydroxyproline per day was detected, and in the pepsin-fluoride group 1.95 (0.50) microg mL(-1). Tissue loss after 9 days in the control group was similar to that in the pepsin group (122.2 (53.4) microm and 122.2 (38.0) microm, n.s., respectively). Fluoridation reduced tissue loss after demineralization (98.8 (30.2) microm) but not after pepsin treatment (125.2 (34.2) microm; p< or =0.05)., Conclusion: Under the conditions used, pepsin had no influence on tissue loss, but altered the efficacy of fluoridation measures.

This study was devised to investigate whether fibrin glue (FG) in combination with growth hormone (GH) could have a beneficial effect at a late period (14 days) after injury. Male Wistar rats, with abdominal sepsis induced by an incomplete anastomosis, were divided into three groups. In the control group, the rats got incomplete anastomoses sutured alone; in the FG and FG/GH groups, anastomoses protection was performed with application of FG alone or in combination with GH. The anastomotic bursting pressure (ABP) was significantly higher in the FG/GH group than that of the FG group on postoperative day (POD) 5 (p < .01), while it could not be measured from POD 7 to POD 14 because of intestinal dehiscence. There was no difference between FG and FG/GH group on POD 3 and POD 5 in anastomotic tensile strength, which was significantly higher in the FG/GH group than that of the FG group from POD 7 to POD 14 (p < .001). Hydroxyproline content of the FG/GH group was significantly higher than that of the control from POD 3 and that of the FG group from POD 5 (p < .05). Combination of FG with GH had a synergistic effect to improve intestinal anastomotic healing over a limited 14-day course of observation.

The aim of this experimental study was to investigate the contribution of insulin-like growth factor I (IGF)-I in the colonic healing process when injected intraperitoneally after colon resection. Forty male Wistar rats were used. Rats in the control group were injected with 3 mL of a solution of 0.9% NaCl intraperitoneally after the operation and on postoperative day 2, 4, and 6. Rats in the IGF-I group received recombinant human IGF-I in a dose of 2 mg/kg body weight intraperitoneally, immediately after the colonic anastomosis was performed and on postoperative day 2, 4, and 6. All rats were killed on postoperative day 7. The hydroxyproline tissue content was significantly higher in the IGF-1 group than in the control group. The bursting pressures were also significantly higher in IGF-1 group than in the control group. The weight change between the groups differed significantly; in the control group the average weight decreased about 5% postoperatively, while in the IGF-1 group the average weight increased about 6%. The average inflammatory cell infiltration score was significantly higher in the control group. Neoagiogenesis did not differ significantly between the two groups. The fibroblast activity differed significantly between the two groups, as the control group had significantly less fibroblasts compared to the IGF-1 group. In conclusion, IGF-I when given intraperitoneally stimulates the healing of colonic anastomoses in the rats. Further studies are required in order to determine whether this effect is dose related.

Purpose: The objective of this study was to assess the effecacy of clip application in the surgical repair of iatrogenic colonic perforations., Material and Methods: Twenty adult male Wistar-Albino rats were divided into two equal groups of ten. In both of the groups an iatrogenic perforation was made in the anti-mesenteric border of the left colon. The defect was closed with interrupted 6/0 polypropylene sutures in group 1 and extraluminal application of vascular clips (VCS--vascular clip system) in group 2. All animals were killed on postoperative Day 4. Wound healing was evaluated with both in situ bursting pressure and hydroxyproline levels., Results: There was no statistically significant difference between the two groups in respect of bursting pressure levels (p = 0.063) whereas hydroxyproline levels were higher in group 2 (p = 0.0021)., Conclusions: Surgical repair of iatrogenic colonic perforations by extraluminal clips gives comparable results according to wound healing parameters. This approach may be a rational alternative to suture or endoscopic repair methods.

Gastrointestinal system anastomoses, especially colonic anastomoses, have significant morbidity and mortality despite recent technical improvements. Besides regulating the circadian rhythm, the pineal gland and its main neurohormone product melatonin have widespread actions in the organism. The purpose of this study was to investigate the effects of pinealectomy on the healing of colonic anastomoses. One hundred male albino Wistar rats were used in this study. The rats were separated into three groups: control, pinealectomy, and sham groups. In the control group, only colonic resection and anastomoses were performed. Following pinealectomy, colonic anastomosis was performed 2 weeks later on one half and 2 months later on the other half of the pinealectomy group. Only craniotomy was performed on the sham group, and the rats were separated and evaluated like the pinealectomy group. Colonic anastomoses were evaluated on postanastomotic day 3 and 7 by measuring the bursting pressure and the hydroxyproline levels in the anastomotic segments. There was no difference in the bursting pressure measurements between the groups on both postoperative day 3 and 7. Although hydroxyproline levels were different between groups on both postanastomotic days 3 and 7, it has been observed that neither normal nor anastomotic hydroxyproline levels influenced the anastomotic bursting pressure measurements. The percent deviation from the normal values was compared in the anastomotic segments, and no differences were found regarding the bursting pressure and hydroxyproline levels. It was concluded that pinealectomy has no effect on the healing of colonic anastomoses.

The purpose of this study was to investigate the efficacy of recombinant human granulocyte/macrophage colony-stimulating factor (rHuGM-CSF) on the wound healing of colonic anastomosis in rats. In total, 40 male Wistar rats were taken into this study. The control group (n = 20) received subcutaneous saline injection. The experiment group (n = 20) received rHuGM-CSF at 100 microg/kg subcutaneously. Both groups underwent colonic anastomosis 2 days later. In each group, burst pressure and hydroxyproline levels were determined 3 and 7 days after anastomosis. White blood cell (WBC) and red blood cell (RBC) counts were determined in each group to evaluate the effect of rHuGM-CSF on hematologic parameters in rats. There was no significant difference between the two groups in regard to burst pressure and hydroxyproline levels (p > .05). As expected, WBC counts significantly increased in the experiment group on days 3 (p = .035) and 7 (p = .046) following surgery. In conclusion, rHuGM-CSF administration and increased WBC counts did not have any positive effect on the wound healing of colonic anastomosis.

1. Using adult Silkie and White Leghorn (WL) chickens, fibre composition and total collagen content were compared between M. iliolibialis lateralis (ITL) and M. pectoralis (PT). 2. Fibres were divided into type IIR and IIW showing strong and weak reduced nicotinamide adenine dinucleotide dehydrogenase activities, respectively. 3. Fibre composition differed markedly between ITL and PT muscle. ITL muscle was composed of both types IIR and IIW fibre but PT muscle of only type IIW Breed difference on composition was noted only in ITL muscle of cocks (type IIR; Silkie 53.8% and WL 37.0%). 4. Total collagen content was greater in ITL muscles and in cocks in both muscles. However, a breed difference was observed only in the PT muscle of hens. 5. In conclusion, the total collagen content was affected by muscle location within the body and by sex rather than by fibre composition.

Purpose: Multi-field radiation therapy for intrathoracic tumours results in a heterogeneous dose distribution in lung tissue. This study investigated whether irradiation of small lung volumes with high fibrogenic doses affects the dose-response relationship for development of fibrosis in distant parts of the ipsilateral lung of mini-pigs., Materials and Methods: The whole right lung of 26 'Mini-Lewe' pigs was irradiated with homogeneous doses of between 25 Gy and 40 Gy given in five equal fractions using opposing anterior-posterior portals and a linear accelerator. Another 32 animals were irradiated with a constant dose of 35 Gy to a small house-shaped high-dose field (base 3.0 cm, height 4 cm) located 3 cm caudolateral to the right hilus, while the surrounding right lung received either no irradiation or homogeneous doses of between 20 Gy and 30 Gy. The radiation fields were simulated and port films were obtained for each of the 10 fields in all pigs. Fibrosis was quantified 9 months after irradiation by determination of the hydroxyproline (HP) content of the 32 high-dose volumes and in the lung apex and the basolateral lung of all 58 pigs. Based on the reference value for the HP-ratio, i.e. the HP-concentration of the right lung over the left lung, obtained in 12 unirradiated control animals, the experimental results were converted into quantal data for probit analysis, a responder being an animal with an HP-ratio > 1.33., Results: A dose-response relationship for the HP-ratio was obtained in the different lung sites and irradiation groups. For a given dose level the mean HP-ratios and response rates did not differ systematically between the lung apex and the basolateral lung. Probit analysis of the pooled data produced ED50 values of 21.8 Gy (95% CI 12-37) for irradiation without a high-dose volume and 25.9 Gy (24-28) for irradiation with a high-dose volume. These values are not significantly different. The results from both irradiation groups could be well fitted by a common dose-response curve with an ED50 value of 26.1 Gy. Unexpectedly, the response rates in the high-dose volume increased with increasing dose to the surrounding right lung. Analysis of the port films provided an explanation for this finding: inaccuracies in daily field positioning. When this error was corrected for by use of the mean dose to the high-dose volume, a dose-response curve with an ED50 of 25.2 Gy (22-29) was determined for the high-dose volume., Conclusions: The results of the study indicate that the irradiation of a small lung volume with high fibrogenic doses does not affect the dose-response relationship for development of fibrosis in distant parts of the ipsilateral lung.

Vitamin A is well recognized as a factor of major importance in epithelial and connective tissue repair mechanisms. Recently it was shown that vitamin A deficiency caused overgrowth and translocation of intestinal bacteria in rats. The aim of this study was to investigate the healing of colonic anastomoses and formation of postsurgical adhesions in vitamin A-deficient germ-free and conventional rats. Fourteen germ-free and 10 conventional rats were allocated to four groups: germ-free rats not given vitamin A, germ-free rats given vitamin A, conventional rats not given vitamin A, and conventional rats given vitamin A. All rats underwent surgery for colonic anastomosis. Seven days afterward, they were euthanized, and the bursting pressure of colonic anastomosis and formation of peritoneal adhesions were evaluated. The bursting pressures in groups not given vitamin A were lower than in groups given vitamin A. The adhesion scores in germ-free groups were lower than in conventional groups. These findings demonstrated that vitamin A had an important role in healing of colonic anastomoses whether in the presence or absence of intestinal flora, and that intestinal bacteria had a greater effect than vitamin A on formation of postsurgical adhesions. This may suggest that the mechanism of healing of colonic anastomoses differs from that of postsurgical adhesion formation.

Unfavourable effects of hypothyroidism and zinc deficiency on wound healing are well known. This experimental study was conducted on rats to evaluate the effects of hormone replacement and zinc supplement on wound healing. A total of 50 rats were divided into 5 groups of 10 rats as follows: Control group (A), a hypothyroidism group (B), a L-thyroxine receiving hypothyroidism group (C), a zinc receiving hypothyroidism group (D), and a L-thyroxine plus zinc receiving hypothyroidism group (E). In order to develop hypothyroidism, 5-propyl 2-thiouracil had been given intraperitoneally for a period of 21 days to all groups except the control group. A laparotomy with a 4 cm median incision was performed in all rats. The first half of the rats was sacrificed on the 7th day and the remaining on the 14th day. Breaking strength, hydroxyproline concentrations in the healing scar tissue and blood serum zinc levels were measured. Although both values--breaking strength and hydroxyproline levels--, compared to all others, were found to be higher in the L-thyroxine plus zinc receiving group (group E) on the 7th day, differences among the groups were not statistically significant. However, on the 14th day, these differences were found to be significant. We conclude that the hormone replacement therapy in hypothyroidism cases was beneficial with regard to wound healing and the results were more satisfactory if zinc was added to the therapy.

The present study was undertaken to further define the role of alveolar macrophages (AM) in the pulmonary response to crocidolite fibers. Briefly, groups of 4 male F344 rats were intratracheally instilled with saline or saline suspensions of crocidolite at 2 or 20 mg/kg body weight. Animals were sacrificed 3, 7, 14, and 28 d after exposure and the lung response was characterized by analysis of bronchoalveolar lavage fluid (BALF) for markers of lung injury and inflammation. AM obtained in BALF were cultured and their production of the pro-inflammatory cytokines, tumor necrosis factor alpha (TNF alpha), and interleukin-1 (IL-1) were characterized along with fibronectin, a protein known to stimulate fibroblast migration and proliferation. Lung hydroxyproline content was determined 28 d after exposure and lung histopathology was characterized on d 28 and 90 after exposure. Crocidolite instillation resulted in transient dose-related pulmonary inflammation as evidenced by increased numbers of BALF neutrophils at the low dose and neutrophils, macrophages, and lymphocytes at the high dose. Cytotoxicity and increased permeability were demonstrated by increased levels of BALF lactate dehydrogenase (LDH) and total protein, respectively. AM TNF alpha and IL-1 production were increased only at the high crocidolite dose. This cytokine response was greatest at d 3 and decreased thereafter. AM TNF alpha and IL-1 release were positively correlated with the increased BALF neutrophils. In contrast to TNF alpha and IL-1, AM fibronectin release was increased at both the low and high doses, with the magnitude of response increasing over time. Consistent with previous acute asbestos inhalation studies, histopathology revealed inflammation localized at the level of the terminal bronchioles and alveolar ducts. Fibrosis was demonstrated at both doses by increased trichrome staining of lung tissue sections. Only the high dose resulted in a detectable increase in lung hydroxyproline. Given the bioactivities of TNF alpha, IL-1, and fibronectin, their increased production after crocidolite exposure indicates they contribute to the pulmonary inflammation and fibrosis occurring with this mineral fiber. In addition, the correlation of increased AM TNF alpha and IL-1 production with increased BALF neutrophils supports a role for these cytokines in crocidolite-induced inflammatory cell recruitment. Lastly, association of a persistent increase in AM fibronectin production with an eventual increase in lung collagen deposition extends the growing database indicating this response is a predictive marker of pulmonary fibrosis.

Chemical and histological indices of liver fibrosis were measured after eight, 18 and 28 weeks in mice infected with Schistosoma mansoni and treated at eight weeks with oxamniquine, in mice infected with S. mansoni and not treated and in mice not infected with S. mansoni. Total worm burdens and liver egg counts were determined in the infected mice to determine severity of infection. Treatment with oxamniquine resulted in near total eradication of S. mansoni worms after 10 weeks and in their complete killing and marked reduction of eggs in the liver at 10 and 20 weeks. Liver fibrosis 10 weeks after oxamniquine treatment was not significantly different than in the untreated, infected group but there was no progression between 10 and 20 weeks after oxamniquine treatment. Fibrosis did however increase between 10 and 20 weeks in the untreated infected group. In the murine model, oxamniquine is an effective treatment for S. mansoni and prevents progression of liver fibrosis.

Objective: To compare the accumulation of collagen in standardised wounds in patients who had abdominal operations and whose postoperative fluid replacement was decided either clinically or by measurements of subcutaneous oxygen tension (PscO2)., Design: Prospective randomised trial., Setting: University Hospital., Subjects: Twenty-nine patients with cancer or inflammatory bowel disease who were undergoing abdominal operations., Interventions: Silicone rubber catheter placed in the upper arm to measure PscO2. Two tubes of expanded polytetrafluoroethylene (ePTFE) implanted subcutaneously parallel to the silicone rubber catheter to measure the amount of collagen accumulated., Main Outcome Measures: Amount of postoperative fluid replacement required in each group, and measurements of hydroxyproline/cm of the ePTFE tubes., Results: The group treated according to PscO2 measurements received more fluid on the day of operation than the group treated according to clinical criteria (p < 0.05). They had accumulated more collagen in their ePTFE tubes by day 7 (p < 0.05)., Conclusion: Replacement of fluid according to measurements of PscO2 rather than by clinical criteria results in improved accumulation of collagen in healing wounds.

Degenerative changes in the temporomandibular joint were induced in 24 rabbits by surgical perforation of the disk. The incongruence obtained between the joint surfaces caused a gradual increase in macroscopic and microscopic changes, including gross remodeling, loss of tissue volume, and altered cell morphology within a 16-week observation period. These changes occurred concurrently with major alterations in the composition of the matrix, as demonstrated by increase in the glycosaminoglycan content of both condylar cartilage and disk and by loss of hydroxyproline in the disk. The lesions in the disk tissue were clearly discernible, whereas those in the condylar cartilage were less extensive. The described method is concluded to give alterations in the temporomandibular tissues, as seen in degenerative joint disease of an early stage.

Inhalation exposure to silicon dioxide is known to result in acute lung injury followed by pulmonary fibrosis. Recently it has been shown that the acute lung damage during influenza virus infection is also followed by a fibrogenic process. To investigate the interaction between silicon dioxide and influenza virus infection, mice were intratracheally instilled with either alpha-quartz or cristobalite and 3 d later infected by aerosol inhalation with influenza A/PR8/34 virus. At 30, 60, and 90 d after infection, groups of virus infected and noninfected mice were sacrificed and their lungs assessed for total and differential lavage cell counts, lung hydroxyproline content, and morphometric analysis. The silica polymorphs did not alter the proliferation of virus in the lungs as quantitated by infectious virus titers of lung homogenates at 1, 5, 7, 10, and 13 d after infection. In noninfected animals, cristobalite was more reactive than alpha-quartz. The virus infection, in all parameters measured at all time intervals, enhanced the overall fibrogenic response of the lungs to the mineral dusts, suggestive of an additive fibrogenic model. The data demonstrate that virus infection following silicon dioxide exposure results in an interaction that leads to an enhanced fibrogenic response.

We studied the influence of controlled micromovements between bone and porous titanium alloy implants with and without hydroxyapatite coating. A dynamically loaded unstable device producing approximately 150-microns axial translation of knee implants during each gait cycle was developed. Stable implants served as controls. Matched stable and unstable implants with either porous titanium (Ti) or hydroxyapatite (HA) coating surrounded by a gap of 0.75 mm were inserted into the weight-bearing regions of the medial femoral condyles in 14 mature dogs. Histologic analysis after 4 weeks showed a fibrous membrane surrounding both types of implants subjected to micromovements, whereas various amounts of bone ingrowth was obtained in the stable implants. The membrane around unstable HA implants was thinner than that around unstable Ti implants. Islands of fibrocartilaginous tissue characterized the membrane around unstable HA implants, whereas fibrous connective tissue surrounded unstable Ti implants. The collagen concentration of the fibrous membranes was higher around unstable HA implants compared with Ti implants. Instability reduced the shear strength of the implants. However, the shear strength of unstable HA implants exceeded that of the Ti implants, both unstable and stable. The greatest shear strength was obtained by stable HA implants, i.e., tenfold greater than that of stable Ti implants. The gap-healing capacity around stable HA implants increased toward the HA surface, and was greater than that around Ti implants. Our study demonstrates that micromovements between bone and implant inhibit bone ingrowth and lead to the development of a fibrous membrane. The superior fixation of unstable HA implants compared with unstable Ti implants may be ascribed to the presence of fibrocartilage, a higher collagen concentration, and radiating orientation of collagen fibers in the membrane. The strongest mechanical anchorage and the greatest amount of bone ingrowth was obtained by stable implants coated with hydroxyapatite.

The right femur in 40 rats was reamed, and in 40 others it was additionally nailed. Analysis of bone blood flow was performed by the distribution of radiolabeled microspheres at different postoperative time intervals. Blood-flow measurements were accompanied by analyses of hydroxyproline and calcium contents. Immediately after reaming, the blood flow of the diaphyseal part of the femur was reduced to approximately one third of that of the intact femur, whereas the contents of hydroxyproline and calcium were reduced by 10 percent. Within 1 week, the blood flow was normal. This study provides evidence that the presence of a nail does not interfere with the restoration of bone blood flow. Restoration of blood flow in bone apparently is a rapid process. The replacement of hydroxyproline and calcium contents seemed to be linked to flow, as no increase in these constituents were found until the blood flow had approximated the level of the intact femur.

This study was undertaken to explore the association between mechanical and chemical effects of intramedullary reaming and nailing. The right femora of 80 rats were reamed and nailed with steel nails. Forty rats were evaluated from 3 days to 24 weeks postoperatively. The other 40 rats had the nail removed after 12 weeks, and they were then followed from 3 days to 24 weeks after nail extraction. Evaluation consisted of in vivo strain recording, geometric measurements, mechanical three-point bending test, and chemical analyses of hydroxyproline and calcium contents. Reaming and nailing caused immediate weakening of the bone as measured by in vitro mechanical tests, but within 3 weeks the mechanical properties were fully restored, whereas in vivo strain remained reduced throughout the experimental period in rats with nails. Removing the nail increased in vivo strain to a level close to that of the intact femur. Remodeling of the bone resulted in greater external anteroposterior diameter, cross-sectional area, area moment of inertia, and amount of hydroxyproline and calcium in the operated on femur as compared with the intact side. This indicates that the repair processes resulted in greater bone mass of the operated on femur than of the intact femur. Thus, there is evidence that nailing techniques effectively assist tissues by repair and remodeling.

We have explored previous findings of remarkably stable in vivo strain at the femoral surface in rats at different ages, and at the same time increased bone stiffness. The rate of collagen synthesis (14C-hydroxyproline/total hydroxyproline ratio) decreased with age, whereas mineralization (calcium/hydroxyproline ratio) increased. Smaller amounts of immature collagen, caused by reduced synthesis, and increased mineralization both probably produce a less flexible material. These chemical alterations support the observed increase in structural stiffness and strength with age. Both mineralization and configurations separately seemed to have effects on in vivo strain. However, none of these variables seemed to be the major determinant for strain.

Use of antineoplastic drugs perioperatively requires an understanding of their potential effects on healing wounds. Adriamycin is an antineoplastic drug with a wide range of antitumor activity. Prior studies have demonstrated that adriamycin impairs skin wound healing but these studies have offered limited explanations for the mechanism of action of the drug vis á vis impairment of healing wounds. In this study we investigated the effect of a xanthine oxidase inhibitor, allopurinol, on adriamycin-induced tissue injury to determine the role oxyradicals might play in reducing wound-breaking strength. Sixty-four Buffalo rats were studied. Eight animals were used to establish drug tolerances. Fifty-six animals were divided into four experimental groups; saline control (2 mL IP), allopurinol control (4.3 mg/kg po), allopurinol-adriamycin (4.3 mg/kg po + 6 mg/kg IV, respectively), and adriamycin (6 mg/kg IV). Animals treated with adriamycin alone had significantly reduced weight at postoperative day (POD) 7 compared to control groups (p less than .025). Bowel-bursting strength (BBS) of the animals treated with adriamycin alone was also significantly decreased at POD 7, compared to controls (p less than .025), and by POD 14 the animals treated with adriamycin alone had a significantly decreased fascial tensile strength, compared to the saline control (p less than .05). At no point did the animals treated with both allopurinol and adriamycin show a significantly decreased weight, BBS, or fascial tensile strength compared to control animals. Allopurinol appeared to protect against adriamycin toxicity on healing wounds. These results suggest that xanthine oxidase and possibly superoxide radicals play an important role in mediating adriamycin toxicity on healing wounds.

The effect of nifedipine, an oral calcium-channel blocker, on adriamycin-induced wound healing was studied. Nifedipine was administered to animals prior to treating with adriamycin. The healing strengths of cecal, fascial, and skin anatomoses were measured. Animals treated with adriamycin alone had significant decreases in healing strength compared to controls: for cecum at postoperative days (POD) 7 and 14; for skin at PODs 14, 21, and 28; for fascia at POD 28. Overall, nifedipine reduced the impact of adriamycin injury on the strength of healing incisional anastomoses. Nifedipine also appeared to protect collagen synthesis at anastomotic sites from adriamycin-induced impairment.

A randomized blind prospective study was carried out to determine if an anabolic androgenic steroid with a high anabolic/androgenic ratio, Group A, (1/0.05) methenolone enanthate (me), compared to an anabolic/androgenic agent with a low anabolic/androgenic ratio, Group B, (1.0/1.0) testosterone propionate (tp), compared to a control, Group C, cottonseed oil (co), affected midhumeral osteotomy healing in 100 two-month-old female Wistar rats. The rats received 4 mg/kg me, 4 mg/kg te, and equal volumes of co weekly. The rats were sacrificed at 2, 4, and 6 weeks. The entire humerus with the healing osteotomy was carefully dissected until all soft tissue attachments were stripped. The healing callus was then subjected to (1) biochemical analysis (hexosamine, hydroxyproline, and calcium), (2) biomechanical testing (progressive distraction of the callus at 1 mm/min on an electrohydraulic materials test system, model 1331, Instron Corp, Canton, MA, and (3) histology. Results of the biochemical testing demonstrated that the percentage of calcium in the healing callus at 2 weeks in group B (tp) was 7.3 +/- 1.0, and this value was greater than that in group C (co), 4.8 +/- 1.6 (p greater than .01), and greater than that in group A (me), 5.6 +/- 0.6 (p greater than .01). At 4 weeks, the percentage of calcium in the callus in group B (tp) was 6.8 +/- 1.9, in group A (me) 7.3 +/- 3.7, and these values were both greater than that in group C (co), 3.9 +/- 2.2 (p greater than .02 and .01, respectively). At 6 weeks the percentage of calcium in the callus in group B (tp) was 11.7 +/- 3.9 and in group A (me) 12.7 +/- 3.9, and again these values were both greater than that in group C (co), 6.7 +/- 2.6 (p greater than .02 and .01, respectively). The remainder of the biochemical analysis, hexosamine and hydroxyproline content, did not show a statistical difference in groups A, B, and C at 2, 4, and 6 weeks. The biomechanical studies and histology also failed to show statistical differences between the three groups at 2, 4, and 6 weeks. The conclusion of this study is that an agent with a low androgenic activity does not increase calcium callus concentrations early in the course of fracture healing compared to an agent with higher androgenic activity. As healing progresses, both agents increase the concentration of calcium in osteotomy healing. The clinical significance of this study is that agents with low androgenic activities favorably influence osteotomy healing and may be clinically useful because they lack unwanted virilizing activity.

Male F344 rats were treated with carbon tetrachloride (CCl4; 0.3 ml/kg per os, 3 times a week) for 2 mo. At the end of the CCl4 administration out of the 65 animals 30 received methylcellulose (MCL; 3.85 ml/kg, 5% solution, per os, 3 times a week) for 6 wk. Thirty-five rats did not receive any further treatment. The fibrotic change caused by CCl4 reached its maximum 2 wk after the end of the treatment. After this, the severity of the fibrotic change regressed spontaneously. This regression was not observable in the liver of rats that received MCL. The fact that MCL is used as a solvent for drugs and as a food additive underlines the importance of the effect of this compound on chronic liver injury.

Immobilization of the knee joint for 9 weeks results in a reduction of the mechanical properties in the lateral collateral ligament. Specifically, ligament stiffness is reduced in this tissue. No statistical change in collagen mass was detected for the medial collateral ligament (MCL) or patellar tendon. An increase in collagen turnover (synthesis and degradation) was, however, found in the immobilized medial collateral ligament and patellar tendon. It is thus proposed that stiffness reduction is due to a change in the ligament substance itself, rather than a result of tissue atrophy.

The modification of early and late radiation damage to the mouse lung by oxygen and WR 2721 has been studied by measurement of breathing rate, lethality, pleural fluid and hydroxyproline content. Protection by hypoxia and sensitization by hyperoxia of early radiation pneumonitis were demonstrated. There was a tendency for the protective effect of WR 2721 to decrease as the breathed oxygen concentration was raised above normal levels. WR 2721 protection of the late damage was higher (PF = 1.6-1.65) than was seen for early pneumonitis (PF = 1.3-1.35) when either breathing rate or lethality were used. Protection factors (PF) gained from measurements of pleural fluid at a year after treatment were similar to those for other endpoints of late damage (PF = 1.7). In contrast, the measurement of fibrosis through determination of lung hydroxyproline at 1 year gave a somewhat lower protection factor for WR 2721. In the same experiments the degree of epilation on the dorsal thorax was scored at 6 weeks. One hundred per cent oxygen gave enhancement (dose enhancement factor (DEF) = 1.2), 9 per cent oxygen reduced damage (DEF less than 0.7) and WR 2721 gave PF values in excess of 1.4 at all oxygen concentrations used. This showed that the radiation response of hair follicles was more sensitive to WR 2721 or to changes of oxygen than the lung. The results presented indicate a competitive interaction between WR 2721 and oxygen for the same injury site causing a shift in the oxygen K curve to higher oxygen concentrations. The validity of applying functional or survival measurements to assess the extent of pulmonary fibrosis is discussed.

The effects of salmon calcitonin (CT) on collagen metabolism and mineral deposition in fractures and intact femora, and on collagen metabolism in healing skin wounds and intact skin have been studied in young male rats. Serum calcium and serum phosphorus were reduced 3 h after the daily subcutaneous CT injection (3 MRC-U/kg body weight), whereas a rebound increase in the serum levels of both minerals was observed at 24 hours after the injection. CT had an early transient inhibitory influence on the collagen synthesis, and this resulted in a reduced total content of collagen in bones and skin specimens from treated rats compared to controls. The concentration of collagen in bone and skin was, however, increased in treated animals compared to controls after prolonged CT administration. Following an early transient increase, the incorporation of strontium-85 into the fractured bones was impaired after 30 days of CT treatment. This resulted in a reduced mineral concentration in the fractures of treated rats compared to controls in the last part of the experiment. The recorded effects of CT treatment, which were most pronounced in healing fractures and intact skin specimens, may be interpreted as an inhibitory influence of CT both on synthesis, mineralization and degradation of collagen.

We describe a model of pulmonary fibrosis in which doses of paraquat ranging from 0.001 mg/kg to 1.0 mg/kg were instilled into the right lung of rats. Lung injury, as measured by right lung lavage albumin content and differential neutrophil count, ranged from undetectable to extremely severe, depending on the dose. Lung fibrosis, as assessed by collagen content and electron microscopy, showed similar dose-response effects. Mortality was minimal. Lavage fibronectin increased after high doses of paraquat, peaked at 2 d postinjury, decreased sharply after 3 d and was normal by 7 d. The temporal pattern was similar to that for albumin. Cultured alveolar macrophages obtained at 4 d postinjury did not have significant increases in fibronectin release. Tissue fibronectin content increased more slowly than lavage fibronectin, peaking at 4 d postinjury, and was still elevated at 7 and 14 d postinjury. Incorporation of [35S]methionine into tissue fibronectin by lung explants obtained at different times postinjury showed a similar time course. Lung collagen content increased steadily between 4 and 14 d postinjury. We conclude that, in our model, graded degrees of lung injury and fibrosis can be produced by varying the dose of unilaterally instilled paraquat and that the increases in lavage fibronectin were related mainly to capillary permeability whereas increases in tissue fibronectin represented parenchymal synthesis. The time course of changes in lung tissue fibronectin and collagen was consistent with the proposed roles of fibronectin in tissue repair and fibrosis. The ability of our model to produce graduated degrees of lung injury and fibrosis should be useful in further studies on the pathogenesis of postinjury lung fibrosis.

Three exposure regimens were used to study the time course of indicators of lung damage and recovery response to single or repeated exposures to phosgene (COCl2). Rats were sacrificed immediately or throughout a 38-d recovery period after inhalation of 1 ppm COCl2 for 4 h, at intervals during a 7-h exposure to 1 ppm phosgene, or at several time points throughout a 17-d exposure to 0.125 and 0.25 ppm COCl2 (4 h/d, 5 d/wk) and during a 21-d recovery period. Regimen 1 revealed significantly elevated lung wet weight, lung nonprotein sulfhydryl (NPSH) content, and glucose-6-phosphate dehydrogenase (G6PD) activity that stayed elevated for up to 14 d. A significant decrease in body weight and food intake was observed 1 d after exposure. Regimen 2 caused a slight depression in NPSH content but did not affect G6PD activity. Regimen 3 animals showed sustained elevations in lung wet weight, NPSH content, and G6PD activity after 7 d of exposure. No significant changes in these endpoints were observed for the 0.125 ppm COCl2 group. No consistent elevation in hydroxyproline content was seen at either exposure concentration. Light microscopic examination of lung tissue exposed to 0.25 ppm COCl2 for 17 d revealed moderate multifocal accumulation of mononuclear cells in the centriacinar region. In summary, exposure to COCl2 caused changes similar in most ways to those observed for other lower-respiratory-tract irritants.

In this paper we discuss the advantages and disadvantages of using histometric and chemical methods for detecting collagenous connective tissue in meat products. Twelve samples of different kinds of smoked sausage meat of known recipe were examined chemically and by two histometric procedures. The results obtained with the histometric procedures were almost identical (r = .96) and there was a strong correlation (r = .88) between the results of one histometric procedure and those obtained with the chemical method. It is concluded that histometric and chemical testing methods are equally valuable in that they both provide an objective quality judgement of the meat under investigation. However, since both methods have certain drawbacks and involve certain errors they should be used in conjunction with each other and not independently. In this way it should be possible to obtain a more complete picture of the composition and/or quality of meats than that obtained via chemical analysis alone.

Bone ingrowth in porous Ti-6Al-4V implants in feline femurs was assessed for the amount and composition 4, 12 and 26 weeks after implantation. During the first 12 weeks there was a rapid ingrowth that levelled out during the ensuing weeks. Bone had penetrated the implants to an average depth of 0.5 mm over their entire surface at 26 weeks. The ingrown bone was deficiently mineralized at 4 and 12 weeks, but reached full mineralization at 26 weeks. A low calcium to phosphorus ratio persisted at all observation times. The ingrown tissue was compared to bone filling drill holes that had been made in the trochanters contralaterally to the implants. By means of radioactive strontium, the mineral deposits in the holes and implants could be compared. The overall results indicate that bone ingrowth in a porous implant and bone healing are similar processes both qualitatively and quantitatively.

We examined quantitatively the ventrodorsal gliding occurring along a sagittal plane in the cricothyroid articulation. For this purpose we used 10 fresh excised human larynges taken at autopsy. Furthermore we examined the morphology, the hydroxyproline content and collagen types of the ligaments and the articular capsule of the cricothyroid articulation. This articulation appeared to be a synovial joint, supported by two ligaments: the lateral and posterior ceratocricoid ligament and articular capsule. The ligaments and the capsule contained both type I and type III collagen fibres and they were rich in elastin fibres 1-2.5 microns in diameter. Ventrodorsal gliding was generally possible when the joint was not rotated to its extremes. The marked individual variation was not essentially affected by sex or age. The collagen content of the lateral ceratocricoid ligament showed a statistically significant negative correlation with the gliding. The articular facet of the cricoid cartilage, which was not usually well-shaped, limits the gliding. A force of +/- 1.0 N caused on the average a change of +/- 1.0 mm in the length of the vocal cord. Further research is needed to evaluate the physiological importance of these findings.

Mice were injected intratracheally with silica or Mt. St. Helens volcanic ash (0.2 mg/g body weight) and examined 6 mo later for changes in pulmonary function, histology, and hydroxyproline content. Results were compared with a similar study using rats. Mice injected with volcanic ash showed significant changes only in wet lung weights. Those injected with silica showed an approximate doubling of lung wet weight and dry weight and hydroxyproline content. Larger increases in lung weight were seen if lymph nodes were left attached. Lung compliance, total lung capacity, and the shape of the pressure-volume curve of the lung were changed as much as 22% in the silica-treated mice. A mild degree of fibrosis with no dense lung consolidation was noted microscopically in silica-treated mice. In contrast, silica-treated rats showed dense lung consolidation, threefold to fivefold increases in both wet and dry lung weights and hydroxyproline content, and up to 40% reductions in pulmonary function measurements. It is concluded that Swiss albino mice develop a milder degree of fibrosis than similarly treated Sprague-Dawley rats and that both biochemical and functional indicators are effective in detecting pneumoconiosis in these species.

The biologic interactions of potentially fibrogenic agents commonly occurring as environmental pollutants remain to be rigorously characterized. Two agents that produce pulmonary fibrosis were selected for this study. Separate groups of male Sprague-Dawley rats were intratracheally instilled with 0, 2, 12, and 50 mg silica and then either sham-exposed or exposed to 0.8 ppm ozone 6 h/d, 5 d/w, for 37 exposure days. Interaction was not detected between silica and ozone in the development of pulmonary fibrosis as determined by quantitative biochemical indices (hydroxyproline and lysyl oxidase) or by histopathologic examination of the lungs. Thus, environmentally relevant levels of ozone appear unlikely to affect the progression of a concurrent silicotic lesion.

The collagen content and the relative distribution of collagen Types I and III were measured in umbilical cords from newborns with congenital dislocation of the hip (CDH) and healthy controls. The total content of collagen per mg dry tissue tended to be reduced. In newborns with CDH the collagen III/I ratio was higher than in the controls. If generalized, these alterations in collagen metabolism may explain the joint hypermobility seen in CDH. It is suggested that the redistribution of collagen Types III and I during normal fetal development and early infancy may be delayed in CDH.