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Background: Worldwide, stroke is the most common cause of death after coronary artery disease (CAD). The risk factor stratification and prognostication of stroke patients are vital in planning and allocating health-care resources. Methods: We conducted a prospective, comparative observational study. Fifty age- and sex-matched cases each of ischemic stroke (IS) and intracerebral hemorrhage (ICH) stroke were enrolled, and baseline demographic, risk factor profile, Glasgow Coma Scale, modified Rankin scale (mRS), and Barthel Index (BI) were recorded, and the cases were followed up for 90 days or till death. We looked at the risk factors associated with IS and ICH and functional outcome of IS vis-à-vis ICH using mRS and BI at 90 days postenrollment. We also compared the mortality of IS vis-à-vis ICH. Results: The presence of hypertension (100% vs. 88%) and smoking (50% vs. 26%) was significantly higher in ICH (P < 0.05). The presence of diabetes mellitus (40% vs. 18%) and CAD (12% vs. 2%) was significantly more in IS cases (P < 0.05). Consumption of alcohol was more prevalent in ICH patients compared to IS patients (30% vs. 24%). Based on mRS and BI at 90 days, ICH cases had significantly poorer functional outcome compared to IS cases (P < 0.0001). Mortality of IS cases (4%) was also significantly less compared to ICH cases (30%). Conclusions: A combination of hypertension, smoking, and history of alcohol consumption had a higher predilection for the occurrence of ICH, whereas a combination of hypertension, diabetes mellitus, and CAD favored the occurrence of IS. The functional outcome of cases of ICH 90 days poststroke was significantly poorer compared to IS cases. The most important factors for poor outcome of ICH cases were more stroke severity at baseline compared to IS cases and the presence of intraventricular hemorrhages in some cases. Mortality was also found to be more in patients with ICH compared to IS.

Free fatty acid receptor 2 (FFAR2) is activated by short-chain fatty acids and expressed widely, including in white adipocytes and various immune and enteroendocrine cells. Using both wild-type human FFAR2 and a designer receptor exclusively activated by designer drug (DREADD) variant we explored the activation and phosphorylation profile of the receptor, both in heterologous cell lines and in tissues from transgenic knock-in mouse lines expressing either human FFAR2 or the FFAR2-DREADD. FFAR2 phospho-site-specific antisera targeting either pSer296/pSer297 or pThr306/pThr310 provided sensitive biomarkers of both constitutive and agonist-mediated phosphorylation as well as an effective means to visualise agonist-activated receptors in situ. In white adipose tissue, phosphorylation of residues Ser296/Ser297 was enhanced upon agonist activation whilst Thr306/Thr310 did not become phosphorylated. By contrast, in immune cells from Peyer’s patches Thr306/Thr310 become phosphorylated in a strictly agonist-dependent fashion whilst in enteroendocrine cells of the colon both Ser296/Ser297 and Thr306/Thr310 were poorly phosphorylated. The concept of phosphorylation bar-coding has centred to date on the potential for different agonists to promote distinct receptor phosphorylation patterns. Here, we demonstrate that this occurs for the same agonist-receptor pairing in different patho-physiologically relevant target tissues. This may underpin why a single G protein-coupled receptor can generate different functional outcomes in a tissue-specific manner.

Introduction: Knee osteoarthritis (OA) is a degenerative condition that is caused by the gradual wear and tear of the cartilage that cushions the bones of the knee. This study will find out the effectiveness of intra-articular hyaluronic acid (IAHA) and intra-articular corticosteroids (IACS) in the management of knee OA. Material & Methods: A randomized control trial was conducted in Hayatabad Medical Complex Peshawar and Pak Military Hospital Rawalpindi from March 2019 to June 2021. Total one eighty-two patients were randomly assessed in the study. Treatment group A received intra-articular hyaluronic acid (IAHA), while treatment group B received intra-articular corticosteroids for three months. This study has used Western Ontario and McMaster Universities Arthritis Index (WOMAC) to evaluate the effectiveness of treatment in both groups of knee OA. Results: The study participants mean age was 56.344 ± 7.25. Out of 182 patients, 2 of the patients reported as “loss to follow up” from IACS Tx group b. Treatment groups include 95 (52.7%) female patient while 85 (47.22%) were male patients. 96 (53.33%) received intra-articular hyaluronic acid (IAHA), while 84 (46.66%) received intra-articular steroids (IACS). The pre- and post-treatment mean difference in WOMAC scores in the hyaluronic acid group was 5.52 ± 4.756, while that in the corticosteroid group was 9.495 ± 1.24 (p value < 0.01). Conclusion: Intra-articular steroids (IACS) and hyaluronic acid (IAHA) alone reduces OA symptoms and pain significantly. Yet intra-articular steroids are more effective than intra-articular hyaluronic acid in reducing symptoms of OA at knee.

Abstract The purpose of the study was to assess both anatomic and functional outcomes between short-pulse continuous wavelength and infrared micropulse lasers in the treatment of DME. This was a prospective interventional study from tertiary care eye hospital—King Khaled Eye Specialist Hospital (Riyadh, Saudi Arabia). Patients with center-involving diabetic macular edema were treated with subthreshold laser therapy. Patients in the micropulse group were treated with the 810-nm diode micropulse scanning laser TxCell (IRIDEX Corporation, Mountain View, CA, USA) (subthreshold micropulse—STMP group). Laser was applied according to recommendations for MicroPulse (125 microns spot size, 300 ms pulse duration and power adjustment following barely visible testing burn) in a confluent mode (low intensity/high density) to the entire area of the macular edema. Patients in the short-pulse group were treated with grid pattern laser with 20 ms pulse PASCAL laser 532 nm (TopCon Medical Laser Systems, Tokyo, Japan) with EndPoint algorithm, which was either 30% or 50% of testing burn (EndPoint 30% and EndPoint 50% groups, respectively). Main outcome measures included best-corrected visual acuity (BCVA in logMAR) and foveal thickness at baseline and the last follow-up visit at 6 months. There were 44 eyes in the micropulse group, 54 eyes in the EndPoint 50% group and 18 eyes in the EndPoint 30% group. BCVA for the whole cohort (logMAR) was 0.451 (Snellen equivalent 20/56) at baseline, 0.495 (Snellen equivalent 20/62) (p = 0.053) at 3 months, and 0.494 (Snellen equivalent 20/62) at the last follow-up (p = 0.052). Foveal thickness for the whole cohort was 378.2 ± 51.7 microns at baseline, 347.2 ± 61.3 microns (p = 0.002) at 3 months, and 346.0 ± 24.6 microns at the final follow-up (p = 0.027). As such the short-pulse system yields more temporary reduction in edema. Comparison of BCVA between baseline and 6 months for EndPoint 30%, EndPoint 50% and STMP groups was p = 0.88, p = 0.76 and p = 0.003, respectively. Comparison of foveal thickness between baseline and 6 months for EndPoint 30%, EndPoint 50% and STMP groups was p = 0.38, p = 0.22 and p = 0.14, respectively. We conclude that the infrared micropulse system seems to improve functional outcomes. When applied according to previously published reports, short-pulse system may yield more temporary reduction in edema while infrared micropulse system may yield slightly better functional outcomes.

Objective: Many studies have described the normal variations in the anatomy of the knee, however very few studies have reported the asymmetry of component size in bilateral total knee arthroplasties. Our study is the first one to find out the incidence of asymmetry of component size in bilateral total knee arthroplasties in Pakistan. Study Design: Place and Duration of Study: Rai Medical College, Sargodha, from Oct 2016 to Oct 2018. Methodology: We conducted a prospective analysis of 100 patients presenting to the orthopedic department of Doctors Trust Teaching Hospital affiliated with Rai Medical College, Sargodha between October 2016 and October 2018. Out of these 89 patients were operated in a single staged procedure whereas 11 were operated in a two staged (second knee at a 2-3 day interval) procedure. Implants used were Nexgen (Zimmer Biomet, Warsaw, IN, USA), Genesis II (Smith and Nephew, Memphis, TN, USA) and PFC-Sigma (DePuy, Warsaw, IN, USA).Data was analyzed using SPSS v.25. Results: Out of 100 patients 20% were found to have component size asymmetry with 12% in the femoral component only, 2% only in tibial component only, 3% in patellar component only, 2% having asymmetry in both femoral and tibial components and 1% having asymmetry in both femoral and patellar components. There was a similar incidence of component size asymmetry in all three different types of implants. Incidence of component size asymmetry in male and female patients was found to be 15.8% and 21% respectively. Conclusion: Since, 20% of the cases showed asymmetry of component size, we recommend that both knees should be measured for implant size individually rather than using the measurement of a single knee for both knees before a bilateral total knee arthroplasty.

Volatile small molecules, including the short-chain fatty acids (SCFAs), acetate and propionate, released by the gut microbiota from the catabolism of nondigestible starches, can act in a hormone-like fashion via specific G-protein-coupled receptors (GPCRs). The primary GPCR targets for these SCFAs are FFA2 and FFA3. Using transgenic mice in which FFA2 was replaced by an altered form called a Designer Receptor Exclusively Activated by Designer Drugs (FFA2-DREADD), but in which FFA3 is unaltered, and a newly identified FFA2-DREADD agonist 4-methoxy-3-methyl-benzoic acid (MOMBA), we demonstrate how specific functions of FFA2 and FFA3 define a SCFA–gut–brain axis. Activation of both FFA2/3 in the lumen of the gut stimulates spinal cord activity and activation of gut FFA3 directly regulates sensory afferent neuronal firing. Moreover, we demonstrate that FFA2 and FFA3 are both functionally expressed in dorsal root- and nodose ganglia where they signal through different G proteins and mechanisms to regulate cellular calcium levels. We conclude that FFA2 and FFA3, acting at distinct levels, provide an axis by which SCFAs originating from the gut microbiota can regulate central activity.

Background: Transcatheter aortic valve replacement (TAVR) is an effective treatment option for patients with severe, symptomatic AS, regardless of the transcatheter heart valve (THV) implanted. Prior studies demonstrated a higher device success with lower paravalvular leak (PVL) using the balloon-expandable (BE) Sapien/XT THV vs. a self-expanding (SE) THV. However, few data are available on the performance of a novel BE THV. Purpose: to compare early clinical performance and safety of the newly available BE Myval THV (Myval, Meril Life Sciences Pvt. Ltd., India) vs. the commonly used SE (Evolut R, Medtronic) THV. Methods: A single-center, retrospective cohort analysis was performed with 166 consecutive patients undergoing TAVR from March 2019 to March 2021 for severe symptomatic AS treated with either the novel BE Myval or the SE Evolut R (ER) bioprosthesis. The primary endpoint was device success at day 30 according to the Valve Academic Research Consortium-3 (VARC-3). Secondary endpoints included 30-day all-cause mortality, cardiovascular mortality, more than mild PVL, permanent pacemaker implantation (PPI) rates and a composite of all-cause mortality and disabling stroke at 6 months. Results: Among the 166 included patients, 108 patients received the SE ER THV and 58 patients were treated with the BE Myval THV. At baseline, the two groups showed comparable demographic characteristics. The primary composite endpoint of early device success occurred in 55 patients (94.8%) in the BE Myval group and in 90 patients (83.3%) in the SE ER group (OR 3.667, 95% CI 1.094–12.14; p = 0.048). At day 30, the BE Myval THV group exhibited a significantly lower incidence of more than mild PVL (BE Myval 3.45% vs. SE ER 14.8%, OR 0.2, 95% CI 0.05–0.8; p = 0.0338), along with a lower rate of PPI (BE Myval 11% vs. SE ER 24.2%, OR 0.38, 95% CI 0.15–0.99; p = 0.0535). At the 6-month follow-up, the incidence of all-cause mortality and disabling stroke did not significantly differ between the two groups, while the incidence of PPI (BE Myval 11% vs. SE ER 27.5%, OR 0.32, CI 95% 0.1273–0.8; p = 0.02) and ≥moderate PVL (BE Myval 6.9% vs. SE ER 19.8%, OR 0.31, 95% CI 0.1–0.94; p = 0.0396) was significantly lower in the BE Myval group. Conclusions: In patients with severe symptomatic AS undergoing TAVR, the novel Myval BE THV provided a comparable performance to the well-known ER SE THV, and it was associated with a lower rate of PPI and ≥moderate PVL within 30 days and 6 months after the procedure. Randomized, head-to-head comparison trials are needed to confirm our results.

Most cases of bladder rupture are traumatic. Spontaneous rupture is much more rare, especially the one due to emphysematous cystitis (EC) which has been reported in only ninth cases in the literature. In our case, we report a 45 years old paraplegic patient with emphysematous cystitis and bladder rupture due to a urinary retention which causes him a urinary peritonitis treated with emergency laparotomy for repairing the wall of the bladder and antibiotics.

Percutanous nephrolithotomy is the gold standard method for large kidney stones currently. It offers high success and low complication rates. Aim There are only a few reports of fractured guidewires inside the pelvicalyceal system, removed with endourology and open surgery techniques, and this is a tour knowledge the first one presenting a broken guidwire in the gerota fat. A 60-year-old man is hospitalized in our department of urology, Mohammed IV university medical center for the management of a PCNL failure in a private clinic.A CT scan showed the presence of a metal device in the gerota fat, we performed an open nephrolithomy, the evolution was favorable. Some equipment used during nlpc can lead to severe issues (broken guidwire and laser fibers) and and open surgery is the only way to resolve the situation.

Patients with lupus anticoagulants are at high risk of systemic arterial and venous thrombosis and arterial stroke. We present an unusual case of a young man presenting inguinal pain. Doppler ultrasound revealed spermatic vein thrombosis on the left side. Hematologic workup revealed positive lupus anticoagulant. The patient was treated with therapeutic heparin.

The chordoma is a very rare notochordal tumor, the cutaneous localization (chordoma cutis) is even rarer and generally follows a local invasion of the integument even a metastasis. The clinical presentation is non-specific and the diagnosis is often late. It is confirmed by the immunohistochemical characteristics of the tumor. Total surgical excision is necessary in order to avoid the local recurrence which represents a frequent character of this tumor. We report the case of a young patient with perineal chordoma evolving from childhood. To our knowledge, our patient represents the first case of chordoma cutis of the perineum without a history of chordoma.

La tumeur de Buschke-Löwenstein appartient au groupe des carcinomes verruqueux. Plus fréquente chez les hommes et les immunodéprimés, elle se développe au niveau génital ou péri-anal, réalisant une volumineuse lésion bourgeonnante parfois ulcérée ou fistulisée aux organes voisins. L´histologie est proche de celle d´un condylome acuminé, avec cependant une prolifération plus marquée et une pénétration profonde dans les tissus adjacents mais sans rupture de la membrane basale. Une infection par Human papillomavirus (HPV) 6 et 11 est volontiers associée à ces tumeurs. La recherche d´autres infections sexuellement transmissibles associées est nécessaire. Un examen clinique rigoureux et une imagerie complémentaire permettent d´établir un bilan lésionnel précis. Le traitement est avant tout chirurgical, et doit être large du fait du haut potentiel récidivant de la tumeur. Des traitements néoadjuvants à type de chimiothérapie ou immunothérapie mériteraient d´être mieux évalués pour limiter le caractère délabrant de la chirurgie.

This is a descriptive prospective study spread over 2 years, involving 30 patients with symptomatic urogenital prolapse, collected at the urodynamic consultation in the urology department at the CHU Mohammed VI in Oujda. The average age is 57 years, the majority of patients had several risk factors for pelvic floor disorders, all patients had a urinary complaint associated with urge prolapse (66.7%), urinary Incotinence iue (63.3%), mixed urinary incontinence (40%), dysuria (40%), and pollakiuria (70%). Twenty six percent point seven had cystocele stage II and 73.3% had cystocele stage III, 26.7% had a prolapse of more than one floor according to the classification of Baden and Walker. Their mean body mass index (BMI) was 27.5 kg/m2. For the urodynamic assessment (BUD): at the flowmeters: dysuria was found in 11 patients (36.7%), with a significant post-voiding residue in 5 patients (16.7%), the normal flow was found in 63.3% of cases. At cystomanometry: bladder hypersensitivity was found in 8 patients (26.7%), reduced bladder capacity in 4 patients (13.3%) and detrusor overactivity in 9 patients (30%). Profilometry had demonstrated sphincter insufficiency in 17 patients (56.7%), whereas it was normal in 13 patients (43.3%). Urodynamic explorations are part of the diagnostic and prognostic elements in the evaluation of bladder and sphincter disorders associated with urogenital prolapse. They make it possible to objectify the impact of prolapse on the bladder sphincter equilibrium.

Nutcracker syndrome (NCS) results most commonly from the compression of the left renal vein by the aorta and vertebral column. Although NCS had been described in many studies, her prevalence is still not known, usual clinical signs are gross hematuria and flank pain. Diagnosis requires a high index of suspicion and treatment consists of a wide range of vascular surgical options with a more recent focus using an endovascular approach. We present a case of a 23-year-old male with intermittent hematuria and flank pain.

The long-term drainage of the urinary tract of patients with unresectable ureteric stenosis, remains a major challenge for urologists. For decades, researchers experimented with different alternatives to the prosthetic ureter with minimal success. However, these patients are offered a minimally invasive procedure in the form of percutaneous nephrostomy or reconstructive surgery. Percutaneous nephrostomy, although minimally invasive, is far from ideal for long-term use. We report the case of a 43-years-old woman who was followed for obstructive renal failure secondary to locally advanced cervical cancer, for which she has benefited a right JJ stent and left nephrostomy. Renal-bladder bypass was indicated as an alternative to nephrostomy. We report on the established implantation procedure and the experiences collected in our service with the Detour® system in the various application areas.

Urinary incontinence is a disastrous complication in men following definitive treatement of prostate cancer or less commonly prostate surgery for benign conditions. In cases where conserative management fails, surgical intervention is indicated. We report our experience in Morocco with artificial sphincter type ZEPHYR ZSI 375 PF in patient with urinary incontinence after radical prostactemy (RP), with discussion of the factors that affect the response rate.

Adrenal myelolipoma (MLS) is a rare, benign and non-functional neoplasm, composed of adipose tissueand myeloid. We report a rare case of adrenal myelolipoma ofa 20-year-old female revealed with chronicabdominal pain. Computed tomography (CT) scan of the abdomen guided diagnosis and surgical resection was performed given symptomatic and bulky mass. Histological examination confirmed the diagnosis. At 18 months after the surgery, the patient had no evidence of recurrence. The diagnosis of MLS is radiological. Therapeutic abstention is the rule for a small, asymptomatic tumors. The surgical removal is indicated when it is bulky (exceeds 7cm), symptomatic or hormonalactivity.

A 68-year-old man presented with priapism and penile gangrene. The patient had no history of penis trauma or medications for erectile dysfunction. Corpus cavernosa aspiration cytology were positive for malignant cells. Total penectomy was performed. Enhanced chest and abdominal computed tomography showed a left renal tumor with pulmonary and hepatic metastases. Ultrasound-guided renal biopsy showed clear cell renal cell carcinoma.

Objective: To evaluate the effect of quadriceps muscle strengthening exercise on quadriceps and hamstring strength ratio in knee osteoarthritis (OA). Methods: This was a quantitative study with quasi-experimental design. The subjects in the study were 16 female patients with knee OA grade 2 and 3. Quadriceps muscle strengthening exercise was given to the subjects 3 times a week during 8 weeks. The study was conducted at the Department of Physical Medicine and Rehabilitation of the Faculty of Medicine, Universitas Padjadjaran-Dr. Hasan Sadikin General Hospital in August–September 2015. Results: It was revealed that the quadriceps muscles improved significantly. However, the hamstring muscles did not show significant improvement based on the comparison between before and after performing the exercise. The average right quadriceps muscle strength before exercise was 12.46 and after exercise was 18. The average left quadriceps muscle strength before and after exercise were 11.59 and 17.7, respectively. The average right hamstring muscle strength before and after exercise were 7.29 and 7.94, respectively. Conclusions: There are quadriceps muscle strength improvements after practicing quadriceps muscle strengthening exercise. However, no significant hamstring muscle strength improvement is seen after practicing quadriceps muscle strengthening exercise. An improvement in quadriceps and hamstring muscle ratio is observed.

Objective: To analyze the correlation between cardiac autonomic neuropathy (CAN) and neutrophil-lymphocyte ratio (NLR) in DM type 2 patients. Methods: This was a cross-sectional study which was conducted at the Internal Medicine Clinic of Dr. Hasan Sadikin General Hospital, Bandung and Chronic Disease Management (CDM) Club in Garut District, West Java, Indonesia from October to December 2015. Subjects were 57 DM type 2 patients who met the inclusion criteria. Cardiac autonomic neuropathy examination and complete blood count (CBC) were performed to discover the subjects’ neutrophil-lymphocyte ratio. Results: A strong correlation was found between CAN in DM type 2 patients and NLR (r=0.679; p=0.000) based on Rank Spearman correlation test. The NLR to CAN cut off point was 1.34. Conclusions: NLR examination can be used as an indicator of CAN in DM type 2 patients with NLR cut off point. There was a correlation between CAN and DM type 2 diagnosis duration.

Background: Polycystic ovarian syndrome (PCOS) and hypovitaminosis D are the two most common endocrine disorders in young women leading to many adverse metabolic consequences. We evaluated the correlation of 25-hydroxy Vitamin D (25OHD) with metabolic parameters and insulin resistance in PCOS. Materials and Methods: We included 100 PCOS patients (age 18–40 years, duration> 6 months) serially, in this cross-sectional study. We excluded patients with past use of insulin sensitizers and hormone therapy. All patients underwent a physical examination, body fat estimation, and a single fasting blood sample was analyzed for the biochemical parameters. The patients were divided into 2 groups as per the 25OHD level: Group 1 (Deficient, 0.05). Conclusion: Hypovitaminosis D is very common in PCOS patients and exacerbates the metabolic abnormalities. It is essential to screen all the PCOS patients for 25OHD deficiency, and further large-scale studies are required to confirm our findings.

A 24-year-old male presented with classic features of the nephrotic syndrome. An initial renal biopsy revealed minimal change disease and thereafter, a second biopsy showed features of focal and segmental glomerulosclerosis. There was no response to conventional immunosuppression, and the patient had to be given rituximab; in spite of this, he went on to develop end-stage renal disease. He continued to have heavy proteinuria leading to severe hypoalbuminemia, thrombosis, infections, and malnutrition, placing the patient in a life-threatening situation. Bilateral renal ablation with embolization of both kidneys with coiling was done at one setting, which finally resolved the proteinuria in the patient. He then underwent a living-related renal transplant, developing recurrence immediately post-transplant. He was again given rituximab along with tacrolimus, mycophenolate mofetil, and prednisolone. There was no response to rituximab, and the patient underwent plasmapheresis, which leads to complete remission. An arteriovenous fistula was created post-transplant to facilitate regular plasmapheresis.

We present a young lady who consumed hair dye, which contained paraphenylene diamine (PPD), as a means of deliberate self-harm. This resulted in severe angio-neurotic edema for which she had to be ventilated, and thereafter developed rhabdomyolysis leading to acute kidney injury (AKI). The unusual aspect was that the patient continued to have flaccid quadriparesis and inability to regain kidney function. Renal biopsy performed 10 weeks after the dye consumption revealed severe acute tubular necrosis with myoglobin pigment casts. This suggests that PPD has a long-term effect leading to ongoing myoglobinuria, causing flaccid paralysis to persist and preventing the recovery of AKI. In such instances, timely treatment to prevent AKI in the form alkalinization of urine should be initiated promptly. Secondly, because PPD is a nondialyzable toxin, and its long-term effect necessitates its speedy removal, hemoperfusion might be helpful and is worth considering

Objective: To compare the effect of overground walking and treadmill exercise on walking speed and ability in elderly from week to week. Methods: This study was conducted in 6 weeks to 18 elderly at Panti Wreda Karitas and Nazareth Bandung (September–December 2011). They were divided into two groups; overground walking exercise group and treadmill group. Walking speed and ability was measured using 10 meter walk test and 6 minute walk test consecutively. Results: Both group walking speed was improved after 1 and 2 weeks exercise (p=0.019 and p=0.050), consecutively. Walking ability in the overground and treadmill group was improved after 1 and 3 weeks exercise (p=0.019 and p=0.009), consecutively. Overground walking group showed greater improvement in walking speed and ability after 3 weeks exercise (p=0.008 and p=0.017) consecutively. Conclusions: Three weeks overground walking exercise improves walking speed and ability better than treadmill exercise.

Cantharidin is an intoxicant found in beetles in the Meloidae (Coleoptera) family. Ingestion may result in haematemesis, impaired level of consciousness, electrolyte disturbance, haematurea and renal impairment. Here, we report two paediatric cases of meloid beetle ingestion resulting in cantharidin poisoning and the clinical presentation of the ensuing intoxication.

This work represents the first study employing non-invasive high-resolution harmonic ultrasound imaging to longitudinally characterize skin wound healing. Burn wounds (day 0-42), on the dorsum of a domestic Yorkshire white pig were studied non-invasively using tandem digital planimetry, laser speckle imaging and dual mode (B and Doppler) ultrasound imaging. Wound depth, as measured by B-mode imaging, progressively increased until day 21 and decreased thereafter. Initially, blood flow at the wound edge increased up to day 14 and subsequently regressed to baseline levels by day 21, when the wound was more than 90% closed. Coinciding with regression of blood flow at the wound edge, there was an increase in blood flow in the wound bed. This was observed to regress by day 42. Such changes in wound angiogenesis were corroborated histologically. Gated Doppler imaging quantitated the pulse pressure of the primary feeder artery supplying the wound site. This pulse pressure markedly increased with a bimodal pattern following wounding connecting it to the induction of wound angiogenesis. Finally, ultrasound elastography measured tissue stiffness and visualized growth of new tissue over time. These studies have elegantly captured the physiological sequence of events during the process of wound healing, much of which is anticipated based on certain dynamics in play, to provide the framework for future studies on molecular mechanisms driving these processes. We conclude that the tandem use of non-invasive imaging technologies has the power to provide unprecedented insight into the dynamics of the healing skin tissue.

While many signals cause upregulation of the pro-inflammatory enzyme cyclooxygenase -2 (COX-2), much less is known about mechanisms that actively downregulate its expression. We have recently shown that the prostaglandin EP1 receptor reduces the expression of COX-2 in a pathway that facilitates its ubiquitination and degradation via the 26S proteasome. Here we show that an elevation of COX-2 intracellular levels causes an increase in the endogenous expression of prostaglandin EP1. The increase in EP1 levels does not occur at the transcriptional level, but is rather associated with complex formation between the receptor and COX-2, which occurs both in vitro and in mammalian tissues. The EP1-COX-2 complex is disrupted following binding of arachidonic acid to COX-2 and accompanied by a parallel reduction in EP1 levels. We propose that a transient interaction between COX-2 and EP1 constitutes a feedback loop whereby an increase in COX-2 expression elevates EP1, which ultimately acts to downregulate COX-2 by expediting its proteasomal degradation. Such a post translational mechanism may serve to control both the ligand-generating system of COX-2 and its reception system.