Inhibitory effects of Serenoa repens on the kinetic of pig prostatic microsomal 5α-reductase activity

The pathogenesis of benign prostatic hyperplasia is linked to the accumulation of dihydrotestosterone (DHT), the active form of testosterone (T), in prostatic tissue. We have defined characteristics of 5α-reductase enzyme which catalyzes the conversion of T into DHT in prostatic microsomes of growing pigs. Peaks for the 5α-reductase activity were found at pH 5.5 and 8.0, which indicates the presence of both type 1 and type 2 isozymes. Kinetic parameters of porcine 5α-reductase in the presence of Serenoa repens extracts revealed uncompetitive, noncompetitive, and mixed types of inhibitions. Our results show the inhibitory action of S. repens on prostate porcine microsomal 5α-reductase activity.     

Endoscopic saphenectomy for coronary artery bypass surgery: comparison of two techniques with and without carbon dioxide insufflation

OBJECTIVE: To compare the clinical results of an initial experience with two techniques of endoscopic saphenectomy with and without gas insufflation. DESIGN: A retrospective study was performed between September 1998 and March 1999 on 40 patients who underwent endoscopic saphenectomy for coronary artery bypass graft without (group 1, n=15) and with (group 2, n=25) carbon dioxide insufflation. INTERVENTIONS: In both groups, the site of harvesting was at the knee through a 2 cm incision. In group 1, dissection was performed using a hand-held dissector while in group 2 dissection was performed after ensuring that there was a seal at the knee and insufflation of carbon dioxide. Collaterals were controlled with an endoclipper in group 1 and bipolar scissors in group 2. Intraoperative procedure time, length of the harvested vein and aspect of the thigh (ecchymosis, hematoma, infection) were recorded. RESULTS: Vein trauma occurred in four patients in group 1 (four of 15, 27%) and in one in group 2 (one of 25, 4%). Hematomas developed in four patients in group 1 (four of 15, 27%) and in one patient in group 2 (one of 25, 4%). Wound infection occurred in no patients in group 1 and in one patient in group 2. One patient in group 2 suffered carbon dioxide embolism with no untoward consequences. Conversion to an open technique was necessary in five patients in group 1 (five of 15, 33%) and in two patients in group 2 (two of 25, 8%). CONCLUSIONS: Endoscopic saphenectomy both with and without carbon dioxide insufflation is associated with a low infection rate, but vein trauma and wound hematomas are more common without carbon dioxide insufflation.     

Localization and characterization of prolactin-like immunoreactivity in the pituitary of the frog Rana ridibunda

Distribution and quantification of PRL in the pituitary gland of the frog Rana ridibunda were investigated using a high-affinity antiserum raised against bullfrog prolactin (PRL). The immunoreactive PRL-producing cells were distributed throughout the pars distalis, the highest density of cells being observed in the rostral region of the adenohypophysis facing the neurointermediate lobe. The dorsal region of the pars distalis contained only a few scattered PRL-immunoreactive cells. At the electron microscopic level, PRL-containing cells were visualized using the immunogold procedure. PRL-immunoreactive material was exclusively stored in secretory granules (size ranging from 200 to 700 nm in diameter). Neither the rough endoplasmic reticulum nor the Golgi apparatus were immunolabeled. Using a radioimmunoassay method we have compared the displacement curves obtained with bullfrog PRL and acetic extracts from Rana ridibunda pituitary. The two binding curves were not completely parallel, suggesting the existence of slight variations of the amino acid sequences of PRL in the two species. The concentration of PRL in the green frog adenohypophysis appeared somewhat higher (35.3 +/- 8.8 micrograms/mg protein) than that in the bullfrog pituitary. These results validate the use of an antiserum to bullfrog PRL to investigate the regulation of PRL secretion in Rana ridibunda.     

Post-cholecystectomy amputation neuroma of the common bile duct with obstructive jaundice

Amputation neuroma of the common bile duct after surgery is a rare and mostly asymptomatic lesion. A 60-year old patient presented with obstructive jaundice three months after a cholecystectomy for symptomatic gallstones. Imaging investigations showed common extrahepatic bile duct stenosis. Surgical resection of the stricture with biliodigestive anastomosis was performed. Histological examination of the surgical specimen revealed an amputation neuroma. Despite its rarity, amputation neuroma of the common bile duct should be considered in patients with post-cholecystectomy syndrome following liver or extrahepatic bile duct surgical procedures.     

Neutral proteases capable of proteoglycan digesting activity in osteoarthritic and normal human articular cartilage

Proteases have been postulated to account for the progressive disappearance of matrix proteoglycans in osteoarthritic (OA) cartilage. The digestion of endogenous proteoglycans by neutral proteases in human OA cartilage homogenates has been measured and compared with that of normal age-matched controls. Cartilage was obtained from 16 patients at the time of knee arthroplasty and from 7 accident victims. Tissue blocks were cut from the tibial plateau; part was used for histologic grading of the severity of OA and part was homogenized for the quantification of neutral metallo- and serine protease activities, based on the release of digested products from endogenous proteoglycans. Total metalloprotease activity (latent plus active forms) was elevated 3- to 10-fold in all diseased cartilage. This elevation was already significant in mild disease, but was greatest in samples of moderate to severe disease. The active form of the enzyme was highest at the center of erosions and decreased in the margins of the plateau. The digestion of proteoglycans, as distinct from their mere release from the tissue, was demonstrated by chromatography on Sepharose-CL2B and by large pore electrophoresis. Serine protease activity on proteoglycans was much lower than that of metalloprotease. The mean activity was highest in mild disease and declined in the severe disease samples, but the difference between these 2 groups and the controls was not statistically significant. The results of this study are consistent with the hypothesis that the neutral metalloproteases of cartilage are involved in the degradation of proteoglycans in osteoarthritis.     

Age-dependent neurological phenotypes in a mouse model of PRRT2-related diseases

Paroxysmal kinesigenic dyskinesia is an episodic movement disorder caused by dominant mutations in the proline-rich transmembrane protein PRRT2, with onset in childhood and typically with improvement or resolution by middle age. Mutations in the same gene may also cause benign infantile seizures, which begin in the first year of life and typically remit by the age of 2 years. Many details of PRRT2 function at the synapse, and the effects of mutations on neuronal excitability in the pathophysiology of epilepsy and dyskinesia, have emerged through the work of several groups over the last decade. However, the age dependence of the phenotypes has not been explored in detail in transgenic models. Here, we report our findings in heterozygous and homozygous Prrt2 knockout mice that recapitulate the age dependence of dyskinesia seen in the human disease. We show that Prrt2 deletion reduces the levels of synaptic proteins in a dose-dependent manner that is most pronounced at postnatal day 5 (P5), attenuates at P60, and disappears by P180. In a test for foot slippage while crossing a balance beam, transient loss of coordination was most pronounced at P60 and less prominent at age extremes. Slower traverse time was noted in homozygous knockout mice only, consistent with the ataxia seen in rare individuals with biallelic loss of function mutations in Prrt2. We thus identify three age-dependent phenotypic windows in the mouse model, which recapitulate the pattern seen in humans with PRRT2-related diseases.

     

Safety and immunogenicity of the epicutaneous reactivation of pertussis toxin immunity in healthy adults: a phase I,randomized, double-blind,placebo-controlled trial

ObjectivesProtection induced by acellular vaccines can be short, requiring novel immunization strategies. Objectives of this study were to evaluate safety and capacity of a recombinant pertussis toxin (PTgen) -coated Viaskin® epicutaneous patch to recall memory responses in healthy adults.MethodsThis double-blind, placebo-controlled randomized trial (Phase I) assessed the safety and immunogenicity of PTgen administered on days 0 and 14 to healthy adults using Viaskin® patches applied directly or after epidermal laser-based skin preparation. Patch administration was followed by Boostrix®dTpa on day 42. Antibodies were assessed at days 0, 14, 28, 42 and 70.ResultsAmong 102 volunteers enrolled, 80 received Viaskin-PT (Viaskin-PT 25 μg (n = 25), Viaskin-PT 50 μg (n = 25), laser + Viaskin-PT 25 μg (n = 5), laser + Viaskin-PT 50 μg (n = 25)), Viaskin-placebo (n = 10) or laser + Viaskin-placebo (n = 2). Incidence of adverse events was similar across groups (any local event: 21/25 (84.0%), 24/25 (96.0%), 4/5 (80.0%), 24/25 (96.0%), 8/10 (80.0%), 10/12 (83.0%), respectively). Direct application induced no detectable response. On day 42, PT-IgG geometric mean concentrations were significantly higher following laser + Viaskin-PT 25 μg and 50 μg (139.87 (95% CI 87.30–224.10) and 121.76 (95% CI 95.04–156.00), respectively), than laser + Viaskin-placebo (59.49, 95% CI 39.37–89.90). Seroresponse rates were higher following laser + Viaskin-PT 25 μg (4/5 (80.0%), 95% CI 28.4–99.5) and 50 μg (22/25 (88.0%), 95% CI 68.8–97.5) than laser + Viaskin-placebo (0/12 (0.0%), 95% CI 0.0–26.5).ConclusionsViaskin-PT applied after laser-based epidermal skin preparation showed encouraging safety and immunogenicity results: anti-PT booster responses were not inferior to those elicited by Boostrix®dTpa. This study is registered at ClinicalTrials.gov (NCT 03035370) and was funded by DBV Technologies.     

The safety of hand‐assisted laparoscopic living donor nephrectomy: The Ohio State University experience with 1500 cases

Hand‐assisted laparoscopic donor (HALD) nephrectomy has been performed at our institution since December 1999. Through May 2014, a total of 1500 HALD procedures have been performed. We have evaluated the outcomes of HALD. The HALD procedure consists of a hand‐port incision as well as two 12‐mm ports. Mean donor age was 40.8 ± 10.8 yr, BMI was 27.9 ± 5.0, there were 541 males, 1271 Caucasians, and the left kidney was removed in 1236 patients. All procedures were successfully completed. Four donors (0.27%) were converted to an open technique due to bleeding. Four donors required blood transfusions. 53 donors (3.5%) were readmitted in the first month post‐donation; almost half were due to gastrointestinal complaints. Six donors required reoperation; three for SBO and three for wound dehiscence. 27 patients (1.8%) developed incisional hernias. Seven donors (0.47%) developed bowel obstruction. All donors recovered well with a mean hospital stay after donation of 2.1 ± 0.3 d. All except one kidney were successfully implanted. Twenty‐one recipients (1.4%) experienced DGF. Ureter complications occurred in 17 (1.1%) recipients. Early graft loss occurred in 13 patients (0.9%). In conclusion, HALD is a safe procedure for the donor with good recipient outcomes.