NAIP Gene Deletion and SMN2 Copy Number as Molecular Tools in Predicting the Severity of Spinal Muscular Atrophy.

Spinal muscular atrophy (SMA) is one of the most prevalent autosomal recessive illnesses with type I being the most severe type. Genomic alterations including survival motor neuron (SMN) copy number as well as deletions in SMN and Neuronal Apoptosis Inhibitory Protein (NAIP) are greatly implicated in the emergence of SMA. However, the association of such alterations with the severity of the disease is yet to be investigated. This study was directed to elucidate the molecular assessment of NAIP and SMN genomic alterations as a useful tool in predicting the severity of SMA among patients. This study included 65 SMA pediatric patients (30 type I and 35 type II) and 65 healthy controls. RFLP-PCR was employed to determine the genetic polymorphisms of the SMN1, SMN2, and NAIP genes. In addition, qRT-PCR was used to identify the expression of the SMN1 and SMN2 genes, and serum levels of creatine kinase were measured using a colorimetric method. DNA sequencing was performed on some samples to detect any single nucleotide polymorphisms in SMN1, SMN2, and NAIP genes. All SMA patients had a homozygous deficiency of SMN1 exon 7. The homozygous deficiency of SMN1 exons 7 and 8, with the deletion of NAIP exon 5 was found among the majority of Type I patients. In contrast, patients with the less severe condition (type II) had SMN1 exons 7 and 8 deleted but did not have any deletions in NAIP, additionally; 65.7% of patients had multiple copies of SMN2. Analysis of NAIP deletion alongside assessing SMN2 copy number might enhance the effectiveness of the diagnosis that can predict severity among Spinal Muscular Atrophy patients.

MLIF Modulates Microglia Polarization in Ischemic Stroke by Targeting eEF1A1.

Monocyte locomotion inhibitory factor (MLIF) is a heat-stable pentapeptide from Entamoeba histolytica. Our previous study found that MLIF protects against ischemic stroke in rats and mice and exerts a neuroprotection effect in human neuroblastoma SH-SY5Y cells. Microglia/macrophage polarization has been proven to be vital in the pathology of ischemic stroke. Nevertheless, whether MLIF is able to modulate microglia/macrophage polarization remains unclear. We performed middle cerebral artery occlusion (MCAO) on C57BL/6J male mice and induced cultured BV2 microglia by oxygen-glucose deprivation (OGD), respectively. Immunfluorescence was utilized to detect the M1/2 markers, such as CD206 and CD16/32. qPCR and ELISA were used to detect the signature gene change of M1/2. The MAPK and NF-κB pathway associated proteins were measured by Western blot. To identify the protein target of MLIF, a pull-down assay was performed. We found that MLIF promoted microglia transferring from a "sick" M1 phenotype to a "healthy" M2 phenotype in vivo or in vitro. Furthermore, we proved that eukaryotic elongation factor 1A1 (eEF1A1) was involved in the modulation of microglia/macrophage polarization. Knocking down eEF1A1 by siRNA exhibited the M1 promotion effect and M2 inhibition effect. Taken together, our results demonstrated MLIF modulated microglia/macrophage polarization by targeting eEF1A1 in ischemic stroke.

Synergistic protective effect of Beta vulgaris with meso-2,3-dimercaptosuccinic acid against lead-induced neurotoxicity in male rats.

Lead (Pb) toxicity is one of the most prevalent causes of human neurotoxicity. The available chelator drugs used now have many adverse effects. So, in this study, the protective role of Beta vulgaris juice (BVJ) on rat neurotoxicity induced by Pb was evaluated and the results were compared with the results of dimercaptosuccinic acid (DMSA, as used drug). Additionally, the synergistic effect of BVJ and DMSA against Pb-induced neurotoxicity was assessed. The study focused on the determination of the antioxidant, anti-inflammatory, and neurological potential of BVJ (alone, and with DMSA) towards lead-induced neurotoxicity. Also, the characterization of BVJ was studied. The results showed that BVJ contains considerable quantities of polyphenols, triterpenoids, and betalains which play an important role as antioxidants and anti-inflammatory. BVJ exhibited a protective effect against neurotoxicity via the reduction of Pb levels in blood and brain. Moreover, BVJ decreased the oxidative stress, inflammation, and cell death induced by Pb. Also, BVJ regulated the activities of acetylcholine esterase and monoamine oxidase-A which changed by Pb toxicity. BVJ and DMSA combination displayed a synergistic antineurotoxic effect (combination index ˂ 1). These results were in harmony with brain histopathology. Conclusion: BVJ has a powerful efficacy in the protection from brain toxicity via diminishing Pb in the brain and blood circulation, resulting in the prevention of the oxidative and inflammatory stress. Treatment with BVJ in combination with DMSA revealed a synergistic effect in the reduction of neurotoxicity induced by Pb. Also, the antioxidant and anti-inflammatory effects of the BVJ lead to the improvement of DMSA therapy.

Sub-micron moulding topological mass transport regimes in angled vortex fluidic flow.

Shear stress in dynamic thin films, as in vortex fluidics, can be harnessed for generating non-equilibrium conditions, but the nature of the fluid flow is not understood. A rapidly rotating inclined tube in the vortex fluidic device (VFD) imparts shear stress (mechanical energy) into a thin film of liquid, depending on the physical characteristics of the liquid and rotational speed, ω, tilt angle, θ, and diameter of the tube. Through understanding that the fluid exhibits resonance behaviours from the confining boundaries of the glass surface and the meniscus that determines the liquid film thickness, we have established specific topological mass transport regimes. These topologies have been established through materials processing, as spinning top flow normal to the surface of the tube, double-helical flow across the thin film, and spicular flow, a transitional region where both effects contribute. The manifestation of mass transport patterns within the film have been observed by monitoring the mixing time, temperature profile, and film thickness against increasing rotational speed, ω. In addition, these flow patterns have unique signatures that enable the morphology of nanomaterials processed in the VFD to be predicted, for example in reversible scrolling and crumbling graphene oxide sheets. Shear-stress induced recrystallisation, crystallisation and polymerisation, at different rotational speeds, provide moulds of high-shear topologies, as 'positive' and 'negative' spicular flow behaviour. 'Molecular drilling' of holes in a thin film of polysulfone demonstrate spatial arrangement of double-helices. The grand sum of the different behavioural regimes is a general fluid flow model that accounts for all processing in the VFD at an optimal tilt angle of 45°, and provides a new concept in the fabrication of novel nanomaterials and controlling the organisation of matter.

Measurement of serum interferon alpha in Egyptian patients with systemic lupus erythematosus and evaluation of its effect on disease activity: a case-control study.

Much evidence highlighted the role of interferon alpha (IFN-α) in systemic lupus erythematosus (SLE) and suggested its possible role in assessing disease activity. We measured serum IFN-α in Egyptian SLE patients in order to determine a cutoff value that can be used to distinguish patients from healthy controls and explored its clinical value in monitoring disease activity and different aspects of the disease, in particular lupus nephritis. This cross-sectional, case-control study was conducted on 59 SLE patients and 30 healthy controls. Serum IFN-α was measured in all participants using sensitive enzyme-linked immunosorbent assay (ELISA). SLE patients underwent assessment of disease activity using the SLE disease activity index-2000 (SLEDAI-2K) as well as an evaluation of proteinuria, complement C3 and C4, and serology. Patients with evidence of renal involvement underwent renal biopsy. The median serum IFN-α was 81.8 pg/mL (interquartile range [IQR] 63.4:102.4), which was significantly higher than in healthy controls (median 10.3 pg/mL [IQR 7.3:11.6]) (p<0.001). At serum level of 14.7 pg/mL, IFN-α has high sensitivity and specificity to discriminate SLE patients from controls, with high positive and negative predictive values. Serum IFN-α was not associated with markers of disease activity, clinical features and anti-double stranded DNA. Furthermore, it was not associated with markers of renal activity, including proteinuria, C3 and C4 complement factors and histopathology renal classes. Despite elevated levels of serum IFN-α in SLE patients, it is not possible to use it as a biomarker for disease activity.

The synergistic hepatoprotective potential of Beta vulgaris juice and 2,3- dimercaptosuccinic acid in lead-intoxicated rats via improving the hepatic oxidative and inflammatory stress.

BACKGROUND: Lead (Pb) is observed in all areas of the environment, mainly derived from human operations such as mining, processing, and burning fossil fuels. Pb toxicity is one of the most prevalent causes of human hepatotoxicity. The available chelator drugs used now have many adverse effects and therefore the world is looking for natural and secure alternatives. METHODS: Here, we evaluated the hepatoprotective role of the oral administration (1 g/kg b.w.) of the lyophilized Beta vulgaris juice (BVJ) against Pb-induced rat hepatotoxicity. We also examined the possible synergistic hepatoprotective impact of the combination between BVJ and 2,3- dimercaptosuccinic acid (DMSA, the currently approved drug for Pb-toxicity). The evaluation depends on the ability of BVJ, DMSA, or their combination (BVJ-DMSA) to reduce serum and hepatic Pb level and to avoid oxidative stress and inflammation caused by Pb. The level of lipid peroxidation, reduced glutathione (GSH), total antioxidant capacity, and the activity of the antioxidant enzymes were quantified. In addition, the level of interleukin (IL)-6, nitric oxide (NO), DNA fragmentation, and liver histology were studied. RESULTS: The results showed that BVJ contained considerable amounts of betalains, vitamin C, and various types of phenolic compounds. Therefore, BVJ displayed a significant (p < 0.05) preventive influence on the elevation of Pb levels in blood and liver as well as the hepatic DNA fragmentation. In addition, it significantly (p < 0.05) improved most of the studied antioxidant and inflammatory markers in the Pb-intoxicated rats. However, the combined extract (BVJ-DMSA) revealed synergistic (combination index < 1) activities in most of the tested parameters. The histopathological results verified the biochemical findings of this research. CONCLUSION: BVJ has a potent efficiency in the protection from Pb-induced hepatotoxicity through the reduction of its accumulation in blood and liver and the prevention of the oxidative stress and inflammation induced by Pb. Additionally, the treatment of hepatotoxicity with BVJ and DMSA in combination showed a synergistic effect and reduced the adverse effects induced by DMSA. Thus, BVJ can be a promising hepatoprotective extract against lead toxicity and its combination with DMSA potentiates this effect.

Patterns of renal involvement in a cohort of patients with inflammatory bowel disease in Egypt.

BACKGROUND AND STUDY AIM: Renal complications are frequent extraintestinal manifestations in inflammatory bowel disease (IBD). We aimed in our study to describe the spectrum of renal affection in our IBD patients. PATIENTS AND METHODS: This study is a retrospective analysis of renal biopsies done for IBD patients who developed renal diseases, at Cairo University Hospital, from June 2005 to Jan. 2016. Results : Among 896 IBD patients, 218 patients (24.3%) developed renal affection. The onset of renal disease mandated renal biopsy at 5.6 ± 7.4 years after IBD diagnosis. Nephrotic range proteinuria was the most common indication for a renal biopsy [81 (37.15%) patients]. Amyloidosis was the most common renal pathological diagnosis [56 patients (25.7%)] followed by immunoglobulin A (IgA) nephropathy [35 patients (16.1%)], focal segmental glome- rulosclerosis (FSGS) [32patients (14.7%)], crescentic glomerulonephritis (CGN) [32 patients (14.7%)], membranous nephropathy (MN) [18 patients (8.25%)], minimal change disease [17 patients (7.7%)], chronic interstitial nephritis (CIN) [10 patients (4.6%)], acute tubular necrosis (ATN) [8 patients (3.7%)], thrombotic microangiopathy (TMA) [6 patients (2.75%)], and acute interstitial nephritis (AIN)[4 patients (1.8%)]. Variable renal histopathology diagnoses did not correlate with age, duration of IBD diagnosis, or drugs used for IBD treatment. Crescentic GN was significantly correlating with ASCA, ANCA-p, and ANCA-c in serum. CONCLUSION: Amyloidosis is a common renal pathological diagnosis in our patients, and is followed by IgA nephropathy, and FSGS.

Retrospective analysis of nephritis response and renal outcome in a cohort of 928 Egyptian lupus nephritis patients: a university hospital experience.

Aim We aim to describe the pattern of response to treatment in a cohort of Egyptian lupus nephritis (LN) patients and to define variable prognostic factors. Methods We retrospectively analyzed records of 928 systemic lupus erythematosus (SLE) patients (898 females, 30 males) with biopsy-confirmed LN seen between 2006 and 2012 at Cairo University hospitals. Results Our study involved 928 SLE patients with a mean age of 26.25 ± 6.487 years, mean LN duration at time of renal biopsy 6.48 ± 4.27 months, mean SLEDAI 28.22 ± 11.7, and mean follow-up duration of 44.14 ± 17.34 months. Induction treatment achieved remission in 683 patients. Remission was achieved in all 32 patients with class II LN, compared to 651/896 (72.7%) patients in classes III, IV, and V. Induction by intravenous (IV) cyclophosphamide achieved response in 435/575 (75.7%) patients, while induction by mycophenolate mofetil (MMF) resulted in response in 216/321 (67.3%) patients ( p = 0.0068). Nephritic flares were least observed when MMF was used for maintenance (30/239 (12.6%) patients), compared to 71/365 patients (19.5%) ( p = 0.0266) when azathioprine (AZA) was used, and 22/79 patients (27.8%) ( p = 0.002) with IV cyclophosphamide. Class IV LN, high chronicity index, presence of crescents, and interstitial fibrosis in biopsies were all associated with chronic kidney disease (CKD) development eventually ( p < 0.001, p = 0.005, p = 0.012, and p = 0.031, respectively). By the end of the study duration, 305 (32.7%) patients had CKD. Logistic regression detected that high baseline serum creatinine, failure to achieve remission, hypertension, and nephritic flare were the main risk factors for poor renal outcome ( p < 0.001, p < 0.001, p = 0.004, and p < 0.001, respectively). The 5 years' mortality was 69 (7.4%) patients with sepsis being the main cause of death. Conclusion IV cyclophosphamide superseded as induction treatment, while MMF was the best maintenance treatment. High serum creatinine, hypertension, and nephritic flare were the main risk factors for poor renal outcome.

First report of MIRU-VNTR genotyping of Mycobacterium avium subsp. paratuberculosis isolates from Egypt.

Mycobacterium avium subsp. paratuberculosis (MAP) is the causative agent of Johne's disease, an economically important disease in ruminants worldwide. It was first isolated in Egypt in 2005. Since then, the pathogen has been detected in different Egyptian provinces. In order to trace the source of infection, genotyping using simple methods of high discriminatory power such as mycobacterial interspersed repetitive unit-variable number tandem repeats (MIRU-VNTR) were carried out in different countries. Until now there is no published information about MIRU-VNTR genotyping of MAP isolates in Egypt. To address that point, 100 faecal samples were collected and cultivated from 3 different suspected dairy farms. Fourteen isolates belonging to one farm were identified as MAP and subjected to genotyping using 8 different MIRU-VNTR loci PCRs. Two different genotypes were recognized based on size polymorphism observed in one locus (VNTR-7) that was confirmed by sequencing. Our work provides a preliminary basis of constructing a MIRU-VNTR genotyping database of MAP in Egypt.

Elective surgery cancelation on day of surgery: An endless dilemma.

BACKGROUND: Cancelation of surgery is a constant agonizing dilemma for nearly all healthcare services that has been intensively investigated to find out its roots, consequences, and possible solutions. The rates of cancelation of surgery vary between centers and more so among surgical specialties with numerous reasons standing behind this phenomenon. PATIENTS AND METHODS: In the current study, analysis of monthly cancelation rates from January 2009 to December 2012, and assessment of establishing new operating rooms (ORs) using statistical process control charts was conducted. A detailed review of a total of 1813 cases canceled on the day of surgery from January to December 2012, to examine the various reasons of cancelation among surgical specialties. RESULTS: The average cancelation rate was 11.1%, which dropped to 9.0% after launching of new theaters. Four reasons explained about 80% of cancelations; Patients "no show" was the leading cause of cancelation (27%). One-fourth of cancelations (24.3%) were due to the need for further optimization, and the third most prominent cause of cancelation was a lack of OR time (19.5%). Unavailability of staff/equipment/implants accounted for only 0.7% of cancelations. The no show was the most common cause of cancelation among all surgical specialties ranging from 21% for plastic surgery to 32% in ophthalmic surgeries. CONCLUSION: It was confirmed that there is a unique profile of cancelation of surgery problem for every institute, an extension of infrastructure may not be the only solution. Control charts helped to enhance the general picture and are functional in monitoring and evaluating changes in the cancelation of surgery.

Review article: health benefits of some physiologically active ingredients and their suitability as yoghurt fortifiers.

The article is concerned with health benefits of two main physiologically active ingredients namely, Isoflavones and γ-Aminobutyric acid, with emphasis on their fitness for fortification of yoghurt to be consumed as a functional food. Isoflavones (ISO) are part of the diphenol compounds, called "phytoestrogens," which are structurally and functionally similar to estradiol, the human estrogen, but much less potent. Because of this similarity, ISO were suggested to have preventive effects for many kinds of hormone-dependent diseases. In nature, ISO usually occur as glycosides and, once deconjugated by the intestinal microflora, the ISO can be absorbed into the blood. At present, it seems convincing their possible protective actions against various cancers, osteoporosis and menopausal symptoms and high levels of blood cholesterol as well as the epidemiological evidence. Γ-Aminobutyric acid (GABA), it is an amino acid that has long been reported to lower blood pressure by intravenous administration in experimental animals and in human subjects. GABA is present in many vegetables and fruits but not in dairy products. GABA was reported to lower blood pressure in people with mild hypertension. It was suggested that low-dose oral GABA has a hypotensive effect in spontaneously hypertensive. Yoghurt beyond its ability to be probiotic food via its culturing with the gut strains, it could further carry more healthy benefits when it was fortified with physiological active ingredients, especially GABA versus ISO preferring, whether, bacteriologically or biochemically, a fortification level of 50 mg ISO/kg or 200 mg GABA/kg.

Pulmonary arterial hypertension in Saudi Arabia: Patients' clinical and physiological characteristics and hemodynamic parameters. A single center experience.

AIMS: The main objective of this study is to describe patients' clinical characteristics and physiological and hemodynamic parameters at the time of diagnosis in a pulmonary hypertension center in Saudi Arabia. MATERIALS AND METHODS: This study reports the results from a single pulmonary hypertension specialized center in Riyadh, Saudi Arabia, namely Prince Sultan Medical Military City/Cardiac Center (PSMMC & CC). Both newly diagnosed (incidence) and referred (prevalence) cases of pulmonary arterial hypertension are included. All characteristics, including clinical, physiological, and hemodynamic parameters at the time of diagnosis are described. RESULTS: A total of 107 patients were identified as having pulmonary arterial hypertension as diagnosed by right heart catheterization. The mean age at diagnosis was 36 (± 9) years, and there was a female preponderance of 62.6%. The mean duration between symptom onset and diagnosis was 27.8 (± 9.0) months. At the time of enrollment, 56.1% of patients were in functional class III and 16.8% were in functional class IV. Fifty five patients (51.4%) were diagnosed as idiopathic pulmonary arterial hypertension, 29 patients (27.1%) as congenital heart disease associated with pulmonary arterial hypertension, 16 patients (15.0%) as connective tissue diseases associated with pulmonary arterial hypertension, 4 patients (3.7%) as heritable pulmonary arterial hypertension, and 3 patients (2.8%) as portopulmonary hypertension. CONCLUSION: This data highlights the current situation of pulmonary arterial hypertension in Saudi Arabia. Our patients are much younger than patients described in other international registries but still detected as late in the course of the disease. A majority of patients displays severe functional and hemodynamic compromise.

Health stimulating properties of the most popular soft cheese in Egypt Kariesh made using skimmed milk UF-retentate and probiotics.

BACKGROUND: Soft skimmed-milk cheese Kariesh is the most popular soft cheese in Egypt. In the past, Karish cheese was traditionally produced by the random fermentation of milk speared its cream layer by the gravity force. Recently, its production has been carried out by several manufacturing procedures using, ultrafiltration (UF) - skimmed milk retentate, certain bacterial cultures, enzymatic coagulation, etc. Therefore, the biological and nutritional evaluations are required. The present study was conducted to evaluate the properties of such cheese coagulated using different procedures involving probiotic strains with emphasis on some chemical and biological attributes. METHODS: Kariesh cheeses were manufactured without whey drainage from UF cow's skimmed milk concentrate coagulated either by 3% yoghurt bacterial starter culture (YC), 3% probiotic starter culture (ABT type) or 2.5% glucono delta lactone (GDL) added whether separately or incorporated with rennet (0.05ml/kg) to achieve the acidic-enzymatic coagulation in comparison with those made conventionally using unconcentrated milk coagulated either by 2% of YC or ABT added whether separately or incorporated with rennet (0.25 ml/kg). Due to the fact that whey is naturally needed to drain in the conventional (C) procedure, the use of GDL as coagulant was eliminated. RESULTS: The obtained results indicated that the application of UF-technique in Kariesh cheese industry was associated with significant increments in the values of protein, ash and pH. Moreover, the electrophoretical patterns of UF-Kariesh cheese obtained with the incorporation between YC, ABT or GDL and rennet were distinguished with the presence of the band of glycomacropeptide, which is normally lost in the whey through the C-procedure. Furthermore, the food intake (FI), body weight gain (BWG), food efficiency ratio (FER),triglycerides (TG), total cholesterol (TC), high density lipoproteins (HDL), total, as well as ionized Ca of blood and the count of lactic acid bacteria of feces of rats were significantly heightened, while low density lipoprotein (LDL) level was lowered as they fed on UF-cheeses, especially when coagulated using ABT, those caused the strongest persistence against the rat colon tumor, which was induced by the injection with 1,2 di-methyl hydrazine. The use of ABT led to raise the dry matter (DM) and ash of Kariesh cheese. Also, the FI, BWG, FER, TG, total, as well as ionized Ca of blood and the count of lactic acid bacteria of feces of rats were significantly increased, while TC, HDL and LDL of blood, as well as coliform count of feces of rats were significantly declined. The incorporation of enzymatic with acidic coagulation in Kariesh cheese manufacture increased significantly the values of ash and pH. However, the cheese figures of DM, protein and titratable acidity were decreased. Also, the values of FI, BWG, FER, TC, HDL, LDL and feces LAB of rats were lowered. Whilst, the values of TG, total as well as ionized Ca and feces coliform of rats were increased.

Sero-prevalence of avian influenza in animals and human in Egypt.

In opposite to most countries, avian influenza virus H5N1 became endemic in Egypt. Since, its first emerge in 2006 in Egypt, the virus could infect different species of birds and animals and even human. Beside the great economic losses to the local poultry industry in Egypt, the virus infected 166 confirmed human cases, 59 cases ended fatally. In the present study, the persistence of the avian influenza in the Egyptian environment was studied. For this purpose, serum samples were collected from human, cattle, buffaloes, sheep, goat, horses, donkeys, swine, sewage rats, stray dogs and stray cats. The sera were collected from Cairo and the surrounding governorates to be examined for the presence of anti-H5N1 antibodies by Haemagglutination Inhibition Test (HI) and ELISA test. Clear differences in the seroprevalence were noticed among different species and also between the results obtained by both techniques indicating the difference in test accuracy. The present data indicate wide spread of the H5N1 virus in the Egyptian environment.

Stability-indicating spectrophotometric and spectrofluorimetric methods for determination of alfuzosin hydrochloride in the presence of its degradation products.

Validated stability-indicating spectrophotometric and spectrofluorimetric assays (SIAMs) were developed for the determination of alfuzosin hydrochloride (ALF) in the presence of its oxidative, acid, and alkaline degradation products. Three spectrophotometric methods were suggested for the determination of ALF in the presence of its oxidative degradation product; these included the use of zero order (0D), first order (1D), and third order (3D) spectra. The absorbance was measured at 330.8 nm for (0D) method, while the amplitude of first derivative (1D) method and that of third derivative (3D) method were measured at 354.0 and 241.2 nm, respectively. The linearity ranges were 1.0-40.0 microg/ml for (0D) and (1D) methods, and 1.0-10.0 microg/ml for (3D) method. Two spectrofluorimetric methods were developed, one for determination of ALF in the presence of its oxidative degradation product and the other for its determination in the presence of its acid or alkaline degradation products. The first method was based on measuring the native fluorescence of ALF in deionized water using lamda(excitation) 325.0 nm and lamda(emission) 390.0 nm. The linearity range was 50.0-750.0 ng/ml. This method was also used to determine ALF in human plasma with the aid of a suggested solid phase extraction method. The second method was used for determination of ALF via its acid degradation product. The method was based on the reaction of fluorescamine with the primary aliphatic amine group produced on the degradation product moiety. The reaction product was determined spectrofluorimetrically using lamda(excitation) 380.0 nm and lamda(emission) 465.0 nm. The linearity range was 100.0-900.0 ng/ml. All methods were validated according to the International Conference on Harmonization (ICH) guidelines, and applied to bulk powder and pharmaceutical formulations.

Human vasal changes after vasectomy: in vitro studies.

UNLABELLED: Failure to impregnate, after successful vasovasostomy, has been attributed to immunologic, testicular, and epididymal factors. OBJECTIVES: To study the effect of vasectomy on human vas innervation and vesicoelastic properties. METHODS: Vas rings were obtained from 8 healthy males during vasectomy as controls and compared to those of 3 vasovasostomy patients. The active and passive properties were determined and the cumulative blocking effects of phenoxybenzamine, propranolol, atropine and tetrodotoxin were studied. RESULTS: There was significantly higher rigidity in the vasovasostomy group as compared to the control group but there were similar active forces between the two groups up to 100-120% of stretch. In the control group, phenoxybenzamine blocked 33.3%, propranolol blocked 15.8%, and atropine blocked 36.5% but tetrodotoxin had no further effect. In the vasovasostomy group, phenoxybenzamine blocked 33.3% (similar to control), propranolol blocked 2%, atropine blocked 11.7% and tetrodotoxin blocked 37.1%. CONCLUSIONS: In vasovasostomy group there was increased rigidity without reduction of the active force. There were also decreased cholinergic and possible existence of nonadrenergic noncholinergic neurotransmitters.

Effect of prostaglandin F2 alpha and methylxanthines on enzymic release of bull epididymal spermatozoa in vitro.

The in vitro effect of PGF2 alpha and methylxanthines (theophylline and caffeine) on enzymatic release of bull epididymal spermatozoa was investigated. Epididymal spermatozoa were diluted with egg yolk citrate-based diluent to a concentration of 50 x 10(6) spermatozoa per ml. Aliquots were supplemented with PGF2 alpha at levels of 0, 300, 600 and 1200 micrograms/ml, theophylline or caffeine was added at levels of 0, 500 and 1000 micrograms/ml and incubated at 37 degrees C for 4 h. Spermatozoal motility was decreased with increasing level of PGF2 alpha and the activities of transaminases in the extracellular medium showed a continuous increase. Addition of theophylline or caffeine at both dose levels significantly increased the sperm motility; the activities of transaminases either were not significantly changed or were significantly decreased during the 4 h incubation. These results suggest that supplementation of bull spermatozoa with high levels of PGF2 alpha suppressed motility and induced sperm membrane damage and permeability. However, supplementation of bull spermatozoa with methylxanthines enhanced sperm motility and was not harmful to the integrity of the sperm membrane.

Effect of xylazine in heifers under thermoneutral or heat stress conditions.

A study was performed to assess the effect of xylazine HCl (0.1 mg/kg of body weight, IV) in heifers maintained at thermoneutrality (18 C, 42% humidity) or under heat stress (33 C, 63% humidity) conditions. Xylazine caused 50 and 70% decreases in serum insulin concentrations in the thermoneutral and heat-stressed heifers, respectively. Xylazine-induced hypoinsulinemia was associated with hyperglycemia. In the thermoneutral group, serum glucose concentrations increased from a basal concentration of 75 mg/dl to 150 mg/dl after 15 minutes. In the heat stress group, the serum glucose concentration increased from 65 mg/dl to 105 mg/dl. Hyperglycemia peaked at 2 hours and remained high for 6 hours after xylazine administration. Heat-stressed heifers took a longer time (107 minutes) to stand than did heifers under thermoneutral conditions (41 minutes). The time to regain sensation to pain was significantly prolonged in heat-stressed heifers. Xylazine had no effect on body temperature and respiration rate in heifers under the thermoneutral condition, whereas it markedly induced hyperthermia and suppressed respiration rate in the heat-stressed heifers. Furthermore, the pulse rate was slightly decreased in thermoneutral heifers and was markedly decreased in the heat-stressed heifers.

Chronic obstructive mastitis in the camel. A clinicopathological study.

Unilateral chronic mastitis in three she camels was due to obstruction of the teat canal by keratin. This lead to dilatation of the ducts, retention of milk and secondary bacterial infection. The teat canals and dilated ducts were lined by stratified squamous epithelium. There was excessive periductal fibrosis. Pasteurella hemolytica was isolated from one animal and Staphylococcus aureus from another. The fluid from the third animal was sterile. The condition was treated successfully by surgical amputation of the affected halves of the udder.