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OBJECTIVE: Recent evidence suggests that non-alcoholic fatty liver disease is associated with diet. Our aim was to investigate the dietary patterns of a Brazilian population with this condition and compare them with the recommended diet. METHODS: A cross-sectional study was conducted on 96 non-alcoholic fatty liver disease patients before any dietetic counseling. All patients underwent abdominal ultrasound, biochemical tests, dietary evaluations, and anthropometric evaluations. Their food intake was assessed by a semi-quantitative food-frequency questionnaire and 24-hour food recall. RESULTS: The median patient age was 53 years, and 77% of the individuals were women. Most (67.7%) participants were obese, and a large waist circumference was observed in 80.2% subjects. Almost 70% of the participants had metabolic syndrome, and 62.3% presented evidence of either insulin resistance or overt diabetes. Most patients (51.5, 58.5, and 61.7%, respectively) exceeded the recommendations for energy intake, as well as total and saturated fat. All patients consumed less than the amount of recommended monounsaturated fatty acids, and 52.1 and 76.6% of them consumed less polyunsaturated fatty acids and fiber, respectively, than recommended. In most patients, the calcium, sodium, potassium, pyridoxine, and vitamin C intake did not meet the recommendations, and in 10.5-15.5% of individuals, the tolerable upper limit intake for sodium was exceeded. The patients presented a significantly high intake of meats, fats, sugars, legumes (beans), and vegetables and a low consumption of cereals, fruits, and dairy products compared with the recommendations. CONCLUSIONS: Although patients with non-alcoholic fatty liver disease exhibited high energy and lipid consumption, most of them had inadequate intake of some micronutrients. The possible role of nutrient-deficient intake in the development of non-alcoholic fatty liver disease warrants investigation.

OBJECTIVE. Existing scoring systems for the diagnosis of group A streptococcus pharyngitis are insensitive or inapplicable in low-resources settings. Bacterial cultures and rapid tests can allow for antibiotic prescription abstention in high-income regions. These techniques are not feasible in many low-resources settings, and antibiotics often are prescribed for any pharyngitis episode. However, judicious antibiotics prescription in the community also is of concern in low-income countries. The objective of this study was to develop a clinical decision rule that allows for the reduction of empirical antibiotic therapy for children with pharyngitis in low-resources settings by identifying non-group A streptococcus pharyngitis. PATIENTS AND METHODS. We prospectively included children with pharyngitis in 3 public hospitals of Brazil during 9 months in 2004. We filled out clinical questionnaires and performed throat swabs. Bilateral [chi square] (2-tailed test) and multivariate analysis were used to determine score categories. The outcome measures were sensitivity, specificity, positive likelihood ratio, and posttest probability of non-group A streptococcus infection with the clinical approach as compared with throat culture. RESULTS. A total of 163 of the 220 children had non-group A streptococcus pharyngitis (negative culture). We established a 3-questions decision rule (age and viral and bacterial signs) with 3 possible answers. The use of this score would prevent 41% to 55% of unnecessary antimicrobial prescriptions. The specificity of the score for non-group A streptococcus pharyngitis was >84%. CONCLUSION. Such a clinical decision rule could be helpful to reduce significantly unnecessary antibiotic prescriptions for pharyngitis in children in low-resources settings. KEY WORDS. pharyngitis, practice guidelines, antibiotic use, developing countries., PEDIATRICS 2006;118:e1607-e1611. URL: www.pediatrics.org/cgi/doi/10.1542/peds.2006-1025 Pierre Robert Smeesters, MD, Dioclecio Campos, Jr, MD, PhD, Laurence Van Melderen, PhD, Eurico de Aguiar, MD, Jean Vanderpas, MD, PhD, Anne Vergison, [...]

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OBJECTIVE: Our objective was to develop an easy, safe, pragmatic, clinical scoring system that would allow decreases in unnecessary treatment with antimicrobial agents in low-resource settings. METHODS: Children with pharyngitis were enrolled prospectively from 2 public hospitals and 1 medical unit in Brasilia, Brazil, over 17 months. Attending clinicians completed a questionnaire and a previously published scoring system for pharyngitis before performing throat swabs and group A streptococcus (GAS) rapid antigen-detection tests. Data from this study were added to those collected in 2004, to assess the performance of each item of the scoring system. The performance of the new clinical decision rule was determined with a receiver operating characteristic curve. The final outcome of the model was assessed on the basis of sensitivity, specificity, and positive likelihood ratio for non-GAS infections with the clinical approach, compared with throat culture or rapid antigen-detection test results. RESULTS: A total of 576 children were included, among whom 400 had non-GAS pharyngitis. The use of our new clinical decision rule would allow for 35% to 55% antibiotic reduction, with 88% specificity. CONCLUSIONS: This clinical decision rule could reduce unnecessary antibiotic treatment significantly in low-resource settings. [ABSTRACT FROM AUTHOR]

Objective: To test the hypothesis that pregnancy is a risk factor for toxoplasmosis seroconversion. Materials and methods: A prospective observational study of women at child-bearing age vulnerable to Toxoplasma gondii. Serological reactions with indirect immunofluorescent antibody and immunoenzyme tests were used. The risk estimate used limits of reliability at 95%, and the results were validated by χ2 and RR tests. Results: Acute infection among pregnant women was 8.6% (45/522), and pregnancy was confirmed to be a risk factor for seroconversion (P=0.001). Living in close contact with host animals and vehicles of oocyst transmission proved to be a statistical risk for pregnant women to seroconvert, which was aggravated in adolescents. Conclusion: Gestation, potentiating susceptibility to this infection, points to the need of primary and secondary prevention for all pregnant women at risk. [Copyright &y& Elsevier]

The decision whether endosomes enter the degradative or recycling pathway in mammalian cells is of fundamental importance for pathogen killing, and its malfunctioning has pathological consequences. We discovered that human p11 is a critical factor for this decision. The HscA protein present on the conidial surface of the human-pathogenic fungus Aspergillus fumigatus anchors p11 on conidia-containing phagosomes (PSs), excludes the PS maturation mediator Rab7, and triggers binding of exocytosis mediators Rab11 and Sec15. This reprogramming redirects PSs to the non-degradative pathway, allowing A. fumigatus to escape cells by outgrowth and expulsion as well as transfer of conidia between cells. The clinical relevance is supported by the identification of a single nucleotide polymorphism in the non-coding region of the S100A10 (p11) gene that affects mRNA and protein expression in response to A. fumigatus and is associated with protection against invasive pulmonary aspergillosis. These findings reveal the role of p11 in mediating fungal PS evasion., Competing Interests: Declaration of interests The authors declare no competing interests., (Copyright © 2023 The Author(s). Published by Elsevier Inc. All rights reserved.)

Reactive oxygen species (ROS) are an essential component of the host defense against fungal infections. However, little is known about how common genetic variation affects ROS-mediated antifungal host defense. In the present study, we investigated the genetic factors that regulate ROS production capacity in response to the two human fungal pathogens: Candida albicans and Aspergillus fumigatus. We investigated fungal-stimulated ROS production by immune cells isolated from a population-based cohort of approximately 200 healthy individuals (200FG cohort), and mapped ROS-quantitative trait loci (QTLs). We identified several genetic loci that regulate ROS levels (P < 9.99 × 10 -6 ), with some of these loci being pathogen-specific, and others shared between the two fungi. These ROS-QTLs were investigated for their influence on the risk of invasive pulmonary aspergillosis (IPA) in a disease relevant context. We stratified hematopoietic stem-cell transplant (HSCT) recipients based on the donor's SNP genotype and tested their impact on the risk of IPA. We identified rs4685368 as a ROS-QTL locus that was significantly associated with an increased risk of IPA after controlling for patient age and sex, hematological malignancy, type of transplantation, conditioning regimen, acute graft-versus-host-disease grades III-IV, and antifungal prophylaxis. Collectively, this data provides evidence that common genetic variation can influence ROS production capacity, and, importantly, the risk of developing IPA among HSCT recipients. This evidence warrants further research for patient stratification based on the genetic profiling that would allow the identifications of patients at high-risk for an invasive fungal infection, and who would benefit the most from a preventive strategy., (Copyright © 2022 The Authors. Published by Elsevier B.V. All rights reserved.)

Our recent data demonstrate a critical role of the RIG-I-like receptor family in regulating antifungal immunity against Aspergillus fumigatus in a murine model. However, the importance of this pathway in humans and the cell types that use this innate immune receptor family to detect A. fumigatus remain unresolved. In this study, using patients who underwent hematopoietic stem cell transplantation, we demonstrate that a polymorphism in human MAVS present in the donor genome was associated with the incidence of invasive pulmonary aspergillosis. Moreover, in a separate cohort of confirmed invasive pulmonary aspergillosis patients, polymorphisms in the IFIH1 gene alter the inflammatory response, including IFN-responsive chemokines. Returning to our murine model, we now demonstrate that CD11c + Siglec F + alveolar macrophages require Mavs expression to maintain host resistance against A. fumigatus. Our data support the role of MAVS signaling in mediating antifungal immunity in both mice and humans at least in part through the role of MAVS-dependent signaling in alveolar macrophages., (Copyright © 2022 by The American Association of Immunologists, Inc.)

Activation of immune cells in response to fungal infection involves the reprogramming of their cellular metabolism to support antimicrobial effector functions. Although metabolic pathways such as glycolysis are known to represent critical regulatory nodes in antifungal immunity, it remains undetermined whether these are differentially regulated at the interindividual level. In this study, we identify a key role for 6-phosphofructo-2-kinase/fructose-2,6-bisphosphatase 3 (PFKFB3) in the immunometabolic responses to Aspergillus fumigatus. A genetic association study performed in 439 recipients of allogeneic hematopoietic stem cell transplantation (HSCT) and corresponding donors revealed that the donor, but not recipient, rs646564 variant in the PFKFB3 gene increased the risk of invasive pulmonary aspergillosis (IPA) after transplantation. The risk genotype impaired the expression of PFKFB3 by human macrophages in response to fungal infection, which was correlated with a defective activation of glycolysis and the ensuing antifungal effector functions. In patients with IPA, the risk genotype was associated with lower concentrations of cytokines in the bronchoalveolar lavage fluid samples. Collectively, these findings demonstrate the important contribution of genetic variation in PFKFB3 to the risk of IPA in patients undergoing HSCT and support its inclusion in prognostic tools to predict the risk of fungal infection in this clinical setting. IMPORTANCE The fungal pathogen Aspergillus fumigatus can cause severe and life-threatening forms of infection in immunocompromised patients. Activation of glycolysis is essential for innate immune cells to mount effective antifungal responses. In this study, we report the contribution of genetic variation in the key glycolytic activator 6-phosphofructo-2-kinase/fructose-2,6-bisphosphatase 3 (PFKFB3) to the risk of invasive pulmonary aspergillosis (IPA) after allogeneic hematopoietic stem cell transplantation. The PFKFB3 genotype associated with increased risk of infection was correlated with an impairment of the antifungal effector functions of macrophages in vitro and in patients with IPA. This work highlights the clinical relevance of genetic variation in PFKFB3 to the risk of IPA and supports its integration in risk stratification and preemptive measures for patients at high risk of IPA.

Serum amyloid P component (SAP, also known as Pentraxin 2; APCS gene) is a component of the humoral arm of innate immunity involved in resistance to bacterial infection and regulation of tissue remodeling. Here we investigate the role of SAP in antifungal resistance. Apcs -/- mice show enhanced susceptibility to A. fumigatus infection. Murine and human SAP bound conidia, activate the complement cascade and enhance phagocytosis by neutrophils. Apcs -/- mice are defective in vivo in terms of recruitment of neutrophils and phagocytosis in the lungs. Opsonic activity of SAP is dependent on the classical pathway of complement activation. In immunosuppressed mice, SAP administration protects hosts against A. fumigatus infection and death. In the context of a study of hematopoietic stem-cell transplantation, genetic variation in the human APCS gene is associated with susceptibility to invasive pulmonary aspergillosis. Thus, SAP is a fluid phase pattern recognition molecule essential for resistance against A. fumigatus.

Lipid rafts form signaling platforms on biological membranes with incompletely characterized role in immune response to infection. Here we report that lipid-raft microdomains are essential components of phagolysosomal membranes of macrophages and depend on flotillins. Genetic deletion of flotillins demonstrates that the assembly of both major defense complexes vATPase and NADPH oxidase requires membrane microdomains. Furthermore, we describe a virulence mechanism leading to dysregulation of membrane microdomains by melanized wild-type conidia of the important human-pathogenic fungus Aspergillus fumigatus resulting in reduced phagolysosomal acidification. We show that phagolysosomes with ingested melanized conidia contain a reduced amount of free Ca 2+ ions and that inhibition of Ca 2+ -dependent calmodulin activity led to reduced lipid-raft formation. We identify a single-nucleotide polymorphism in the human FLOT1 gene resulting in heightened susceptibility for invasive aspergillosis in hematopoietic stem cell transplant recipients. Collectively, flotillin-dependent microdomains on the phagolysosomal membrane play an essential role in protective antifungal immunity., Competing Interests: Declaration of Interests The authors declare no competing interests., (Copyright © 2020 The Author(s). Published by Elsevier Inc. All rights reserved.)

In response to infection, macrophages adapt their metabolism rapidly to enhance glycolysis and fuel specialized antimicrobial effector functions. Here we show that fungal melanin is an essential molecule required for the metabolic rewiring of macrophages during infection with the fungal pathogen Aspergillus fumigatus. Using pharmacological and genetic tools, we reveal a molecular link between calcium sequestration by melanin inside the phagosome and induction of glycolysis required for efficient innate immune responses. By remodeling the intracellular calcium machinery and impairing signaling via calmodulin, melanin drives an immunometabolic signaling axis towards glycolysis with activation of hypoxia-inducible factor 1 subunit alpha (HIF-1α) and phagosomal recruitment of mammalian target of rapamycin (mTOR). These data demonstrate a pivotal mechanism in the immunometabolic regulation of macrophages during fungal infection and highlight the metabolic repurposing of immune cells as a potential therapeutic strategy.

The identification of patients at higher risk of developing Epstein‑Barr virus (EBV) infection in hematopoietic stem cell transplants (HSCT) is useful for the prevention of EBV‑associated diseases A prospective observational study was developed that included 40 patients (27 male and 13 females, with mean age of 32.2±1.5 years old) undergoing allogeneic‑HSCT between January and December 2015. EBV was examined in whole blood samples collected during routine procedures at day (D)+30, D +60, +90, D+120, D+150 and D+180 post‑transplant. EBV was detected, at least once during the follow‑up period in 70.0% of our patients. Results indicated that patients with unrelated donors had increased risk of developing EBV infection at D+60 and D+150 (OR=3.9, P=0.058; OR=8.0, P=0.043; respectively). Moreover, myeloablative conditioning (OR=4.3, P=0.052), anti‑thymocyte globulin use (OR=12.0, P=0.030) and graft‑vs.‑host disease (OR=6.7, P=0.032) were associated with EBV infection at D+60, D+150 and D+90, respectively. In our series, none of these patients developed post‑transplant lymphoproliferative disease. To the best of our knowledge, the present study is the first study to report EBV infection in patients undergoing aHSCT from Portugal. The study revealed that EBV infection is associated with different factors. These findings provide evidence towards the identification of high‑risk patients for EBV‑infection and associated disease.

Background: Reactivation of latent human cytomegalovirus (CMV) in patients undergoing allogeneic stem-cell transplantation (HSCT) predisposes to several clinical complications and is therefore a major cause of morbidity and mortality. Although pentraxin-3 (PTX3) has been previously described to bind both human and murine CMV and mediate several host antiviral mechanisms, whether genetic variation in the PTX3 locus influences the risk of CMV infection is currently unknown. Methods: To dissect the contribution of genetic variation within PTX3 to the development of CMV infection, we analyzed described loss-of-function variants at the PTX3 locus in 394 recipients of HSCT and their corresponding donors and assessed the associated risk of CMV reactivation. Results: We report that the donor, but not recipient, h2/h2 haplotype in PTX3 increased the risk of CMV reactivation after 24 months following transplantation, with a significant effect on survival. Among recipients with h2/h2 donors, CMV seropositive patients as well as those receiving grafts from unrelated donors, regardless of the CMV serostatus, were more prone to develop viral reactivation after transplantation. Most importantly, the h2/h2 haplotype was demonstrated to display an influence toward risk of CMV reactivation comparable to that conferred by the unrelated status of the donor alone. Conclusions: Our findings demonstrate the important contribution of genetic variation in donor PTX3 to the risk of CMV reactivation in patients undergoing HSCT, highlighting a promising prognostic value of donor PTX3 to predict risk of CMV reactivation in this clinical setting.

Post‑transplant lymphoproliferative disorder (PTLD), despite its rarity, is an important mortality/morbidity event in transplant patients. The purpose of the present study was to retrospectively examine the clinical and pathologic characteristics, and outcomes of PTLD at the Portuguese Oncology Institute of Porto. A retrospective review of patient information was performed for patients that developed PTLD following allogeneic hematopoietic stem cell transplant (aHSCT) and were diagnosed between 2005 and 2012. The present study included a total of 15 patients, 8 females (53.3%) and 7 males (46.7%), with different clinicopathological characteristics. The most frequent clinical condition inducing aHSCT was acute lymphocytic leukemia (40.0%). Conditioning regimens consisted primarily in busulfan and cyclophosphamide, with anti‑thymocyte globulin, and myeloablation was the preferential treatment. Epstein‑Barr virus (EBV) was present in all patients with a median time of diagnosis following transplant of 75 days (range, 25‑485 days) and a median viral load of 4.75 log10 copies/ml (range, 3.30‑6.26 log10 copies/ml). PTLD diagnosis was mainly assessed by clinical findings, and histological confirmation was available for 5 patients: 3 monomorphic, 1 polymorphic and 1 with early lesions of PTLD. To the best of our knowledge, this is the first study to describe PTLD cases in HSCT patients in Portugal. The data reinforces the importance of performing EBV monitoring in high‑risk patients, particularly those receiving a transplant from mismatch/unrelated donors, and those with myeloablative conditioning regimen including antithymocyte globulin. The results also suggested that EBV viral load may be significant for the prediction of PTLD development.

Invasive aspergillosis (IA) is a severe infection that can occur in severely immunocompromised patients. Efficient immune recognition of Aspergillus is crucial to protect against infection, and previous studies suggested a role for NOD2 in this process. However, thorough investigation of the impact of NOD2 on susceptibility to aspergillosis is lacking. Common genetic variations in NOD2 has been associated with Crohn's disease and here we investigated the influence of these  genetic variations on the anti-Aspergillus host response. A NOD2 polymorphism reduced the risk of IA after hematopoietic stem-cell transplantation. Mechanistically, absence of NOD2 in monocytes and macrophages increases phagocytosis leading to enhanced fungal killing, conversely, NOD2 activation reduces the antifungal potential of these cells. Crucially, Nod2 deficiency results in resistance to Aspergillus infection in an in vivo model of pulmonary aspergillosis. Collectively, our data demonstrate that genetic deficiency of NOD2 plays a protective role during Aspergillus infection.

LC3-associated phagocytosis (LAP) is a non-canonical autophagy pathway regulated by Rubicon, with an emerging role in immune homeostasis and antifungal host defence. Aspergillus cell wall melanin protects conidia (spores) from killing by phagocytes and promotes pathogenicity through blocking nicotinamide adenine dinucleotide phosphate (NADPH) oxidase-dependent activation of LAP. However, the signalling regulating LAP upstream of Rubicon and the mechanism of melanin-induced inhibition of this pathway remain incompletely understood. Herein, we identify a Ca 2+ signalling pathway that depends on intracellular Ca 2+ sources from endoplasmic reticulum, endoplasmic reticulum-phagosome communication, Ca 2+ release from phagosome lumen and calmodulin (CaM) recruitment, as a master regulator of Rubicon, the phagocyte NADPH oxidase NOX2 and other molecular components of LAP. Furthermore, we provide genetic evidence for the physiological importance of Ca 2+ -CaM signalling in aspergillosis. Finally, we demonstrate that Ca 2+ sequestration by Aspergillus melanin inside the phagosome abrogates activation of Ca 2+ -CaM signalling to inhibit LAP. These findings reveal the important role of Ca 2+ -CaM signalling in antifungal immunity and identify an immunological function of Ca 2+ binding by melanin pigments with broad physiological implications beyond fungal disease pathogenesis.

The aim of this study was to characterize Human Cytomegalovirus (HCMV) drug resistance mutations in UL97 and UL54 genes in allogeneic hematopoietic stem cell transplant (allo-HSCT) recipients in Portugal. We have performed a retrospective study with 22 patients from a cohort of patients with different haematological malignancies submitted to allo-HSCT between 2010 and 2014. Patients were selected according to clinical and laboratory data of HCMV infection and management. HCMV resistance mutations were characterized by sequencing of UL97 and UL54 genes. Sequence data were compared with: 1) HCMV genome reference strain AD169; and also 2) UL97 from Merlin strain (GenBank: AY446894.2), and UL54 from TB40/E strain (GenBank: ABV71585.1). Resistance mutations were identified in seven patients (32%): five harboured resistance mutations in UL97: A594V (n = 2), C592G (n = 1), L595W (n = 1), and C603W (n = 1); and two harboured resistance mutations in UL54: P522S and L957F, one in each patient. Several natural polymorphisms and unknown mutations were found in both UL97 and UL54, with the majority of the patients harbouring more than one unknown mutation in UL97 but only one in UL54. No simultaneous mutations were found. This is the first study in Portugal to characterize HCMV UL97 and UL54 sequences and to identify HCMV drug-resistance mutations in allo-HSCT patients. The UL97 resistance mutations found were amongst the most frequent resistant mutations, while UL54 L957F mutation was here reported for the first time in a clinical specimen. This information provides important information regarding HCMV strains and antiviral resistance in our population., (Copyright © 2016 Elsevier B.V. All rights reserved.)

Invasive aspergillosis (IA) is a life-threatening fungal disease commonly diagnosed among individuals with immunological deficits, namely hematological patients undergoing chemotherapy or allogeneic hematopoietic stem cell transplantation. Vaccines are not available, and despite the improved diagnosis and antifungal therapy, the treatment of IA is associated with a poor outcome. Importantly, the risk of infection and its clinical outcome vary significantly even among patients with similar predisposing clinical factors and microbiological exposure. Recent insights into antifungal immunity have further highlighted the complexity of host-fungus interactions and the multiple pathogen-sensing systems activated to control infection. How to decode this information into clinical practice remains however, a challenging issue in medical mycology. Here, we address recent advances in our understanding of the host-fungus interaction and discuss the application of this knowledge in potential strategies with the aim of moving toward personalized diagnostics and treatment (theranostics) in immunocompromised patients. Ultimately, the integration of individual traits into a clinically applicable process to predict the risk and progression of disease, and the efficacy of antifungal prophylaxis and therapy, holds the promise of a pioneering innovation benefiting patients at risk of IA.

Cytomegalovirus (CMV) infection is 1 of the leading causes of morbidity and mortality after allogeneic hematopoietic stem cell transplantation (aHSCT), mainly within the first 100 days after transplantation. We aimed to characterize CMV infection in a cohort of 305 patients with different malignancies undergoing aHSCT at the Portuguese Institute of Oncology of Porto between January 2008 and December 2012. In total, 184 patients (60.3%) developed CMV infection, mainly viral reactivations rather than primary infections (96.2% versus 3.8%, respectively). The majority of patients (166 of 184) developed CMV infection ≤100 days after transplantation, with median time to infection of 29 days (range, 0 to 1285) and median duration of infection of 10 days (range, 2 to 372). Multivariate analysis revealed that CMV infection was increased in donor (D)-/recipient (R)+ and D+/R+ (odds ratio [OR], 10.5; 95% confidence interval [CI], 4.35 to 25.4; P < .001) and in patients with mismatched or unrelated donors (OR, 2.54; 95% CI, 1.34 to 4.80; P = .004). Cox regression model showed that the risk of death was significantly increased in patients >38 years old (OR, 1.89; 95% CI, 1.14 to 3.12; P = .0137), who underwent transplantation with peripheral blood (OR, 3.02; 95% CI, 1.33 to 6.86; P = .008), with mismatched or unrelated donor (OR, 2.16; 95% CI, 1.48 to 3.13; P < .001), and who developed CMV infection (OR, 1.76; 95% CI, 1.07 to 2.90; P = .025). Moreover, patients who developed CMV infection had a significantly reduced median post-transplantation survival (16 versus 36 months; P = .002)., (Copyright © 2014 American Society for Blood and Marrow Transplantation. Published by Elsevier Inc. All rights reserved.)

In this article, we report the results of analyses of bone healing around four types of dental implants. Five implants of each type were inserted into the proximal tibia metaphysis of adult New Zealand rabbits and were analyzed using computerized histomorphometry 12 weeks after implantation. Hydroxyapatite-coated implants showed more direct bone contact and more lamellar bone in the threads than the titanium implants. There was a significant correlation between an increase in the percentage of mineralized tissue in the threads of metallic implants and cellular density around the implant, indicating less lamellar bone in contact with metallic implants.

The growth of the rat parotid gland induced by daily treatment with isoproterenol (IPR) for 2 weeks was investigated by stereological methods applied to light microscopy. After 7 days of treatment, the glandular mass presented a 286% growth, with the first 3 days being the period of greatest growth. Total acinar volume exhibited a 363% increase during the period from 0 to 7 days, while acinar-cell volume presented a 468% growth from 0 to 5 days of treatment. On the other hand, total acinar-cell number did not increase during the study period. Thus, under the conditions used, IPR-stimulated gland growth was essentially hypertrophic. However, a significant increase in the number of bipolar and multipolar mitoses was also observed, especially on the third and fifth days of treatment. As no increase in acinar-cell number occurred during growth, the presence of these mitoses suggests that cell death occurred during gland growth. On this basis, bipolar mitoses may occur to replace cells that probably degenerated during treatment, whereas multipolar mitoses may lead to the occurrence of polyploidy.