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Biomedical subjects

S S Ahmed

Publications and source records attributed to S S Ahmed.

At least 19 recordsLinked to original sources

Unusual manifestation of a concurrent demodectic and sarcoptic mange in a Zebu-Friesian cross-bred heifer.

We describe a rare case of a concurrent demodectic and sarcoptic mange in a 2-year-old heifer in Khartoum, Sudan. The lesions were massive lumps of granulomatous tumour-like dermatitis with thick, nodular folds mainly covering the head, neck and shoulders. Histopathological examination of the lesions revealed the presence of both Demodex bovis and Sarcoptes scabiei. The animal died regardless of the anti-parasitic treatment it received.

Animals↗

Behavioral effects of acute and chronic triazolam treatments in albino rats.

Previous behavioral studies on triazolam (TZ), which are small in number, could only speculate about tolerance to the anxiolytic effect of TZ, as the experiments did not cover sufficient time (of 4 to 7 days) for tolerance to develop. Therefore longer time for chronic TZ administration is used. We investigated the effects of TZ on motor activity and exploratory behavior using plus maze and open field. Three experiments were conducted. In the first, five groups of rats were acutely treated with different doses of TZ (0.25 mg/kg-4.0 mg/kg). In the second set of experiments, rats were treated chronically with a single daily dose of TZ (started with 0.25 mg/kg and increased by time to 1.0 mg/kg) for 5 weeks (representing clinical use). In the third, rats were treated chronically with three daily doses of TZ (started with 0.25 mg/kg and increased by time to 0.5 mg/kg) for 20 days (mimicking drug abuse). Acute TZ administration produced dose dependent anxiolytic effects and a decrease in motor activity with higher doses. Chronically treated rats, either once daily or three times daily doses, showed tolerance to both anxiolytic and sedative effects of TZ. It may be concluded that tolerance to the anxiolytic and sedative effects of TZ would develop after chronic administration either with clinical use or its abuse.

Animals↗

Brain glycine levels in triazolam-treated albino rats.

The present study investigates the effects of acute and chronic administration of triazolam in albino rats on glycine levels in different brain areas. Three experiments were conducted. In the first, five groups of rats were acutely treated with different doses of triazolam (0.25 mg/kg-4.0 mg/kg i.p.). In the second experiment, rats were treated chronically by a single daily dose of triazolam (started by 0.25 mg/kg and increased by time to 1.0 mg/kg) for 5 weeks, simulating clinical use. In the third, rats were treated chronically three daily doses of triazolam (started by 0.25 mg/kg and increased by time to 0.5 mg/kg) for 20 days, simulating a form of drug abuse. Brain levels of glycine and plasma levels of triazolam were measured using HPLC technique. The acute triazolam administration produced an increase in glycine levels in almost all brain areas studied. The chronic administration of single daily dose of triazolam produced normal glycine levels in most of the brain areas; this indicates the development of tolerance to glycine content increasing action of triazolam. The chronic administration of three daily doses of triazolam produced a decrease in glycine levels in almost all brain regions studied, which might be a prerequisite for oncoming withdrawal syndrome.

Animals↗

Evolution of hepatitis B virus polymerase gene sequence during famciclovir therapy for chronic hepatitis B.

Prolonged administration of nucleoside analogues for chronic hepatitis B may result in the emergence of hepatitis B viral polymerase mutants. To gain insight into the mechanism involved in the virus's resistance to famciclovir, the amino acid sequences of the terminal protein and reverse-transcriptase (RT) domains of the viral polymerase were determined during therapy among 28 patients. The antiviral response was independent of viral genotypes, and nonresponse to famciclovir was associated with a complex variability of the RT domain. No mutation in the YMDD motif was observed, whereas an L528M mutation was clearly selected by famciclovir treatment in 2 patients, as well as 14 novel mutations in 7 patients. Clone sequence analysis of the RT domains of patients undergoing retreatment with famciclovir and/or lamivudine showed the selection of a preexisting drug-resistant mutant in one case and indicated that sequential antiviral therapy may allow the rapid selection of resistant strains.

2-Aminopurine↗

Effects of acute and chronic triazolam treatments on brain GABA levels in albino rats.

The present study investigated the effects of acute and chronic intraperitoneal administration of Triazolam on g-aminobutyric acid (GABA) levels in different brain areas of albino rats. Three experiments were conducted. In the first, five groups of rats were acutely treated with different doses of Triazolam (0.25 mg/kg-4.0 mg/kg). In the second experiment, rats were treated chronically with a single daily dose of Triazolam (started with 0.25 mg/kg and increased by time to 1.0 mg/kg) for 5 weeks, simulating clinical use. In the third, rats were treated chronically with three daily doses of Triazolam (started with 0.25 mg/kg and increased by time to 0.5 mg/kg) for 20 days, representing a form of drug abuse. Brain levels of GABA and plasma levels of Triazolam were measured using high performance liquid chromatography (HPLC). The acute Triazolam administration produced an increase in GABA levels in all brain areas studied. The chronic administration of single daily dose of Triazolam produced normal GABA levels in all brain areas except brain stem where the levels were significantly decreased; this indicates the development of tolerance to Triazolam action on increasing GABA content. The chronic administration of three daily doses of Triazolam produced a decrease in GABA levels in all brain regions studied. In conclusion, chronic single daily dose treatment (representing normal use) produces tolerance to Triazolam effects on brain GABA levels, while chronic three daily doses administration (akin to drug abuse) causes a fall in GABA levels.

Animals↗

Ribavirin monotherapy in patients with chronic hepatitis C: a retrospective study of 95 patients.

Ribavirin is a purine nucleoside that inhibits the replication of a variety of RNA viruses and was shown to have a transient efficacy in chronic hepatitis C during short-term therapy. We have analysed retrospectively its efficacy in 95 patients with liver biopsy-proven chronic hepatitis C. Patients received oral ribavirin (600-1200 mg daily) for a mean duration of 11 months. Alanine aminotransferase (ALT) levels returned to normal values in 38 patients (40%) and decreased by more than 50% in 20 other patients (21%). HCV RNA clearance from serum was observed in seven patients (8%). The biochemical response rate was higher in patients with chronic hepatitis (54%) than in those with cirrhosis (24%) (P = 0.003). Clearance of HCV RNA was observed in 10% of the patients with chronic hepatitis vs 4% of the patients with cirrhosis. In non-responders to interferon (IFN) therapy, ALT levels returned to normal values in 11 (26%) and HCV RNA became negative in one (2%), as compared to 48% and 3%, respectively, in those contraindicated for IFN. In 17 patients in whom paired liver biopsy specimens were available, the histology activity index (HAI) improved in 12. Therapy was generally well tolerated although 11 patients had to stop therapy because of side-effects, which were more common in cirrhotic patients. In conclusion, our results suggest that long-term administration of ribavirin is well tolerated and may be beneficial in controlling the progression of chronic hepatitis C. This may represent an alternative therapy in patients who have contraindications for interferon therapy or as a palliative approach in non-responders to IFN.

Adult↗

TRAM flap perforator ligation and the delay phenomenon: development of an endoscopic/laparoscopic delay procedure.

Despite its versatility in breast reconstruction, the TRAM flap is at times subject to ischemic compromise, especially in certain high risk populations. A preoperative delay procedure can decrease the likelihood of TRAM flap failure or fat necrosis, but the required extent of this delay procedure is not clearly defined. In an attempt to augment flap vascularity while reducing surgical dissection and morbidity, six distinct delay procedures and a nondelayed control were compared in a rat TRAM flap model (n = 8 for all groups). An important feature that was incorporated into several groups was the ligation of the contralateral rectus perforators through minimal skin incisions (endoscopic analogy, groups 4 to 7). The most effective delay procedure was the combination of contralateral rectus perforator ligation and ipsilateral dominant pedicle ligation (group 7), which was achieved with two minimal skin incisions and no significant flap undermining. This procedure reduced the flap necrosis from 63.2 +/- 5.8 percent (control) to 13.5 +/- 3.3 percent (p < 0.001). After completion of the animal studies, clinical application of a "minimally invasive" TRAM flap delay procedure was then undertaken in eight high risk patients with only modest ischemic compromise. Although the clinical experience is too early to draw definite conclusions, we feel that "endoscopic delay" has potential as a modality that will increase flap vascularity but minimize the morbidity of the preliminary procedure.

Animals↗

Basic aspects of GABA-transmission in alcoholism, with particular reference to GABA-transaminase.

Neuronal dysfunction is the neurobiological basis for alcoholic behaviour, and ethanol craving seems related to hypofunction of the GABA-ergic activity. Gamma-aminobutyric acid (GABA) is the major inhibitory neurotransmitter in the central nervous system (CNS). In several studies, GABA has been shown to be an important target of ethanol in the CNS, partly, as a consequence of damage to membrane-bound enzymes and receptors. GABA is involved in mediating pre- and post-synaptic inhibition of neuronal activity. It is speculated that the initial excitatory effects of ethanol may be due to inhibition of GABA-ergic activity whereas the sedative effects of the higher doses may be mediated by the activation of this inhibitory system. In the CNS, GABA is synthesised from glutamic acid by the enzyme glutamate decarboxylase (GAD) and catabolized into succinic semialdehyde by the enzyme GABA-transaminase (GABA-T), which are pyridoxal phosphate (PLP) dependent enzymes. Platelet GABA-T was characterized as being similar to central GABA-T. Inhibition of GABA-T with certain potent and selective compounds markedly increases the levels of brain GABA. Experimentally, acute ethanol treatment does not alter GABA-T activity whereas chronic treatment produces an increase in the activity, though, with some reservations since a bimodal effect has been found in chronically ethanol-treated rats. Thus, as it will be discussed below, it may be suggested that GABA-T inhibitors (e.g. vigabatrin) could have a potential role in the treatment of alcoholism and in some of the problems of ethanol withdrawal and of other drugs of abuse. Related studies on metabolism and concentrations of GABA are also promising and show a greater increase in our understanding of the aetiology and treatment of ethanol dependence and withdrawal. In general, this article also reviews both the animal and clinical observations in the field of alcoholism with regard to the GABA system.

4-Aminobutyrate Transaminase↗

Timing, magnitude, and utility of surgical delay in the TRAM flap: I. Animal studies.

Surgical delay is an effective technique, but the precise timing of the delay effect and the required extent of the delay procedure are uncertain. We endeavored to study flap survival as a function of the duration of the delay period in a rat transverse rectus abdominis myocutaneous (TRAM) flap model. Two specific delay procedures (limited and extensive) were utilized, and flap survival was assessed after delay periods of 3, 7, 10, 14, 21, and 30 days (n > or = 7, all groups). A delay of 7 days or greater resulted in statistically significant improvement in flap survival in all groups. The delay effect appeared to be maximal at 14 days, and in the extensive delay group, a 14-day delay resulted in statistically greater flap survival than a 7-day delay. Improvement in flap survival was greater when an extensive delay procedure was used. Although the model system has limitations, the rat TRAM flap appears to be a suitable model for the study of the delay phenomenon. Possible clinical correlations are addressed in part II.

Analysis of Variance↗

A new experimental model: the vascular pedicled cutaneous flap over the mid-dorsum of the rat.

The cutaneous vascular anatomy of the mid-dorsum in the rat and its role in flap design was studied in the rat. The investigation consisted of anatomic dissection, methylene blue injection into the axial artery, and flap harvesting in live animals. Dissection and injection revealed that the mid-dorsum of the rat derives its blood supply largely from the 10th intercostal artery, here referred to as the middle dorsal artery, which originates from the lateral aspect of the thoracic aorta. The cutaneous vascular territory of the middle dorsal artery was defined as follows: the medial border, midline of the dorsum; the lateral border, midaxillary line; the cephalic border, a line joining the medial and lateral borders midway between the level of the axilla proximally and 1 cm above the base of the rib cage distally; and the caudal border, a line drawn midway between the latter point proximally and the anterior superior iliac spine distally. Both unilateral and bilateral vascular pedicled island cutaneous flaps were harvested in living rats based on and exceeding the vascular territory delimited by methylene blue injection. Flaps limited to this territory with intact middle dorsal arteries showed total survival, while oversized flaps underwent partial necrosis peripherally. Because of its simplicity, reliability, and consistent vascularity, this flap has potential applications in the study of flap hemodynamics.

Animals↗

Scanning electron microscopy of Diplotriaena obtusa, Henry and Ozoux, 1909 (Nematoda: Diplotriaenidae) from Hirundo saviginii in Egypt.

Out of 152 Egyptian swallows, Hirundo saviginii, 24 were found infected by the nematode Diplotriaena obtusa Henry and Ozoux (1909). The worms were collected from the body cavity of the host. Male and female worms were described by light and scanning electron microscopes as a first record of this nematode from Egypt. The specific characteristics of the nematode were defined, including; anterior and posterior extremities, cuticular surface of the body.

Animals↗

Oxygen radical formation during cytochrome P450-catalyzed cyclosporine metabolism in rat and human liver microsomes at varying hydrogen ion concentrations.

The role of pH in uncoupling the electron-flux between oxidoreductase and cytochrome P450 (P450) or P450 and cyclosporine (CyA) and resulting in the generation of oxygen radicals was investigated in vitro in rat and human liver microsomal preparations. Since the electron-flux from NADPH to cytochrome c via oxidoreductase showed a fairly constant reduction activity from pH 7.0-9.5, the generation of oxygen radicals at the level of P450-Cyclosporine (instead of oxidoreductase-P450) was investigated. The effects of increasing pH on oxygen radical formation was measured by the thiobarbituric acid assay (TBA) and the adrenochrome reaction. The trends in oxygen radical production were correlated with benzphetamine metabolism (production of formaldehyde) and CyA metabolism (analyzed by high performance liquid chromatography). The TBA assay showed increased MDA-detected lipid peroxidation (unrelated to autooxidation) at pH < 8.0 and pH > 8.0 (rat and human, respectively) while the adrenochrome reaction showed decreased oxygen radical production. When these results were compared to benzphetamine (a substrate of P450 2B and 3A) metabolism and CyA (a substrate of P450 3A) metabolism, increased metabolism followed the pH-dependent trend of MDA-detected lipid peroxidation. Benzphetamine metabolism with formaldehyde production and depletion of parent compound during CyA metabolism were increased at pH < 8.0 in the rat samples and at pH > 8.0 in the human samples. This parallel relation suggests that the increased metabolism of CyA at lower pH in rats and higher pH in humans may be the result of favorable interactions of P450 with Cyclosporine that also result in increased oxygen radical-related lipid peroxidation.

Adrenochrome↗

Induction of murine gamma delta T cells cytotoxic for xenogeneic rat cells.

C57BL/6 mice deprived or nondeprived of CD4+ and CD8+ T cells by mAbs were challenged with a rat T cell line, W7TM-1. Spleen cells obtained from CD4- and CD8-depleted animals rejecting W7TM-1 were examined by cytofluorometry, which demonstrated the presence of highly increased gamma delta type CD4-CD8- T cell population (30 to 50% of entire T cells). In vitro sensitization of these spleen cells with W7TM-1 generated a mixture of gamma delta and alpha beta type CD4-CD8- CTL for W7TM-1. Repeated stimulation of these cells with W7TM-1 resulted in a gamma delta-type T cell population with more than 95% purity by day 45. In contrast, alpha beta type CD8+ CTL for W7TM-1 were induced from mice nondeprived of CD4+ and CD8+ T cells. Both gamma delta-type CD4-CD8- CTL and alpha beta type CD8+ CTL were cytotoxic for rat cells in a species-specific manner. However, only reactivity of gamma delta type CD4-CD8- CTL, but not alpha beta type CTL, was inhibited by a mAb for TCR-gamma delta. The gamma delta type CD4-CD8- CTL clones were also prepared from spleen cells derived from CD4- and CD8-depleted mice. They were also reactive for xenogeneic cells in a species-specific manner. Spleen cells derived from CD4- and CD8-depleted mice rejecting the whole-layer rat skin grafts were in vitro sensitized with rat spleen cells, which also generated gamma delta type CD4-CD8- CTL specific for rat cells. V gamma 1 was detected as a major V gamma gene expressed in this gamma delta population by reverse transcriptase-PCR. Cytotoxicity for xenogeneic cells may represent one of major function of gamma delta T cells.

Animals↗

Fc receptors in liver sinusoidal endothelial cells in NZB/W F1 lupus mice: a histological analysis using soluble immunoglobulin G-immune complexes and a monoclonal antibody (2.4G2).

In systemic lupus erythematosus accompanied by the abnormal appearance of circulating immune complexes (ICs), Fc gamma receptor (FcR)-mediated IC handling in macrophages including Kupffer cells has been shown previously. However, sinusoidal endothelial cells (SECs) largely ingest soluble immunoglobulin (Ig) G-ICs through FcRs. In this study, the character, antigenic expression, and activity (i.e., ligand-binding capacity of SEC FcRs in NZB/NZW F1 lupus and NZW nonautoimmune mice) were immunohistochemically analyzed using monoclonal antibody (MAb) 2.4G2 to FcRs and peroxidase-antiperoxidase IgG as a ligand on cryosections. MAb 2.4G2 stained SECs and blocked the ligand binding of SEC FcRs in both mice strains. The staining intensities with MAb 2.4G2 in SECs and the FcR activities in SECs alone and all sinusoidal cells in both mice strains reached their maximum values at the age of 5 months. Staining intensities in NZB/W F1 were significantly higher at 1 and 2 months and lower at 9 months than those in NZW. The number of Kupffer cells detected by MAb F4/80 to macrophages in both mice strains gradually increased until 5 months, but their number in NZB/W F1 at 9 months was twice as large as that in NZW. In conclusion, SEC FcRs in mice are low-affinity FcRs that react with MAb 2.4G2. The data of FcR activity suggest no impairment of the FcR-mediated IgG-IC binding on SECs in NZB/W F1 in early life.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

Basic aspects of GABA-transaminase in neuropsychiatric disorders.

Over the last two decades, there have been several studies suggesting the major inhibitory amino acid neurotransmitter gamma-aminobutyric acid (GABA) is involved directly and/or indirectly in the pathogenesis of many neurologic diseases and psychiatric disorders. GABA is mainly degradated to succinic semialdehyde in a reaction catalyzed by the enzyme GABA-transaminase (GABA-T). Inhibition of this enzyme produces considerable elevation of GABA contents in the brain, and such elevation has been found to correlate with pharmacologic and behavioral effects. We focus attention, from the basic aspects, on brain and platelet GABA-T activities in various species, with a special reference to neuropsychiatric disorders. It seems that the activity of GABA-T in the brain and/or in the blood platelets is correlated to certain neuropsychiatric disorders such as alcoholism, epilepsy, and Alzheimer's disease. In animal and human studies, platelet GABA-T was identified with similar kinetic and inhibitor characteristics to those of the brain. Therefore, in this way, studies of the activity of the enzyme GABA-T in relation to neuropsychiatric disorders could be undertaken to understand, diagnose, and treat GABA-related disorders of the central nervous system.

4-Aminobutyrate Transaminase↗