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Biomedical subjects

M Alam

Publications and source records attributed to M Alam.

At least 145 records · Page 8Linked to original sources
PubMed1995

Anodic voltammetric study of ascorbic Acid at platinum and gold rotating disc electrodes.

Anodic Voltammetry of ascorbic acid at platinum and gold rotating disc electrodes has been examined in acidic and alkaline media. Ascorbic acid is oxidised by a single two electron wave at platinum and one electron two step at gold electrode. The best medium for electroanalysis is 0.1 mol 1(-1) sulphuric acid in which it shows obedience to the Levich relationship at both electrodes. The limiting current is linearly proportional to ascorbic acid concentration with Zero intercept and shows excellent rapid voltammetric determination. Electrode Kinetic parameters for mass and charge transfer have been determined. Voltammetric method has been used to determine the number of electrons involved in the reaction and the reaction mechanism has been elucidated.

Acids↗
PubMed1995

Effects of the peptide release inhibitor, octreotide, on daytime hypotension and on nocturnal hypertension in primary autonomic failure.

OBJECTIVE: To investigate the effects of the somatostatin analogue octreotide, which inhibits the release of various peptides, on 24-h ambulatory blood pressure profiles in subjects with primary (idiopathic) autonomic failure due to sympathetic denervation, and in particular to determine whether octreotide reduces daytime hypotension and whether it causes or accentuates nocturnal hypertension. SUBJECTS AND METHODS: Eighteen subjects with primary autonomic failure, confirmed by detailed physiological and biochemical autonomic tests, were studied in a randomized manner on two occasions, with and without octreotide treatment (1 mu g/kg body weight subcutaneously, twice a day at 0800 and 1800 h). Blood pressure was measured using the SpaceLabs 90207 system. This was connected at 0900 h with programmed recordings at 30-min intervals until 2300 h and at 60-min intervals until the next morning. There were additional subject-initiated recordings after 5 min each of lying, sitting and standing four times during the day, while sitting after lunch at noon and while standing following walking in the evening. Additional analyses included calculation of cumulative sum (cusum)-derived parameters and construction of cusum plots. RESULTS: After octreotide treatment, the overall mean daytime systolic/diastolic blood pressure (mmHg) was raised (123 +/- 2/77 +/- 1 without treatment versus 128 +/- 2/79 +/- 1 with treatment). There was a reduction in postural (supine versus standing: from 96 +/- 3/62 +/- 3 without treatment to 106 +/- 5/67 +/- 4 with treatment), postprandial (107 +/- 3/65 +/- 2 to 122 +/- 5/75 +/- 4) and exertion-induced (96 +/- 5/61 +/- 5 to 113 +/- 6/71 +/- 5) hypotension. Symptoms of hypotension were reduced by octreotide. Nocturnal blood pressure was lower after octreotide (139 +/- 3/84 +/- 1 versus 129 +/- 3/78 +/- 2). Analyses with the cusum technique further demonstrated blood pressure recovery during the day, with a reduction in the magnitude of change at night after octreotide treatment. CONCLUSIONS: In primary autonomic failure, 24-h ambulatory blood pressure profiles and cusum analyses indicate that octreotide has beneficial effects in reducing postural, postprandial and exertion-induced hypotension, without causing or increasing nocturnal hypertension.

Adult↗
PubMed1994

A conformationally defined 6-s-trans-retinoic acid isomer: synthesis, chemopreventive activity, and toxicity.

A conformationally defined retinoic acid analog (1) which contains a dimethylene bridge to maintain the 6-s-trans orientation for two terminal double bonds in the polyene chain was synthesized. A Reformatsky reaction was utilized to extend the polyene chain of the starting enone, which provided exclusively the 9Z-configuration for the intermediate aldehyde. A Horners-Emmons condensation with this aldehyde then produced retinoic acid analogs with both 9Z- and 9Z,13Z-configurations. An I2-catalyzed isomerization of the intermediate 9Z-aldehyde yielded the all-E-aldehyde, which was olefinated as above to yield the (all-E)- and (13Z)-retinoic acid analogs of 1. Each configurational isomer of 1 was evaluated for its ability to inhibit the binding of retinoic acid to CRABP (chick skin) and to inhibit the chemical induction of ornithine decarboxylase in mouse skin. In each assay (all-E)-1 was the most active isomer, and this activity was comparable to or better than that for (all-E)-retinoic acid. (all-E)-1 and (13Z)-1 were both shown to be equally effective as (13Z)-retinoic acid in suppressing the proliferation of human sebaceous cells in vitro. (all-E)-1 was further evaluated for its ability to prevent the induction of mouse skin papillomas and to induce signs of vitamin A toxicity in mice. The cancer chemopreventive activity of (all-E)-1 was comparable to that of (all-E)-retinoic acid, and the toxicity was comparable to or slightly better than that of the natural vitamin.

3T3 Cells↗
PubMed1994

Aminodiol HIV protease inhibitors. 1. Design, synthesis, and preliminary SAR.

A series of HIV protease inhibitors containing a novel C2 symmetrical "aminodiol" core structure were prepared from amino acid starting materials. The ability of the aminodiols to inhibit HIV replication in cell culture is comparable to their ability to inhibit the isolated enzyme, a result compatible with good cell membrane penetration by this class of compounds. Optimization of the structure-activity in this series led to aminodiol 9a (Ki = 100 nM; ED50 (HIV-1) = 80 nM) containing P1/P1 benzyl and P2/P2 Boc substituents. Compound 9a is a selective inhibitor of HIV protease versus other aspartyl proteases such as human renin, human cathepsin D, and porcine pepsin. In addition, 9a is equipotent against HIV-1 and HIV-2 in cell culture and demonstrates similar activity in infected T-lymphocytes and PBMCs. After i.v. and oral administration in rats, 9a displayed significant oral bioavailability (ca. 40%) and a promising plasma elimination half-life (4 h).

Amino Alcohols↗
PubMed1994

Identification of volatile forms of methyl groups released by Halobacterium salinarium.

halobacterium salinarium (formerly H. halobium) is a chemotactic and phototactic archaeon from which volatile methyl groups are released continually, a phenomenon related to its sensory system. We found that released methyl groups comprised two different chemical species, methanol and methanethiol, the sulfur analog of methanol. Radiolabeling experiments showed that the methyl groups of both compounds, as well as the sulfur of methanethiol, were derived from methionine but were donated to cellular components and subsequently cleaved to produce the respective volatile compounds. Previous work had shown that chemostimuli and photostimuli result in transient increases in the rate of release of volatile methyl groups. We found that these increases reflected increased release of methanol but not of methanethiol. Thus, the methyl group chemistry of the H. salinarium sensory system is analogous to the well-studied chemotactic system of Escherichia coli. The reactions that result in methanethiol release are of unknown function and have unusual features. They may involve a methionine-gamma-lyase activity we detected in H. salinarium. Sulfur derived from methionine was found attached to specific proteins in reduction-sensitive disulfide linkages.

Carbon-Sulfur Lyases↗
PubMed1994

Divergent effects of intravenous dobutamine and nitroprusside on left atrial contribution to ventricular filling in dogs with chronic heart failure.

The left atrial (LA) contribution to left ventricular (LV) filling is often attenuated in patients with heart failure. It remains uncertain, however, whether therapy with positive inotropic agents or vasodilators improves or further impairs this maladaptation. In the present study, the effects of intravenous dobutamine and nitroprusside on the LA contribution to LV filling was examined in seven dogs with chronic heart failure produced by multiple sequential intracoronary microembolizations. Pulsed Doppler echocardiography was used to measure mitral inflow velocity before and after an intravenous infusion of dobutamine (4 micrograms/kg/min) and an intravenous infusion of nitroprusside (3 micrograms/kg/min). The percent LA contribution to LV filling was calculated as the ratio of the time-velocity integral of the LA component of mitral inflow velocity (Ai) to the time-velocity integral of total diastolic inflow velocity (Ti) times 100. Dobutamine increased LV filling pressure, LV end-diastolic wall stress, LV end-diastolic stiffness, and Ei, but had no effect on Ai or the percent LA contribution to filling (14% +/- 3% vs 12% +/- 2%) (p < 0.34). In contrast, nitroprusside decreased LV filling pressure, LV end-diastolic wall stress, and end-diastolic stiffness, and increased Ei, Ai, and the percent LA contribution to LV filling (12% +/- 2% vs 17% +/- 2%) (p < 0.01). The results indicate that dobutamine and nitroprusside have divergent effects on the LA contribution to LV filling. In dogs with chronic heart failure, dobutamine appears to impair LA contribution to the LV filling by augmenting LA workload, whereas nitroprusside appears to elicit greater LA contribution to LV filling by reducing the LA workload.

Animals↗
PubMed1994

Microflora modulates endocrine cells in the gastrointestinal mucosa of the rat.

BACKGROUND/AIMS: Gastrointestinal peptides and biogenic monoamines participate in the regulation of gastrointestinal functions. The aim of this study was to examine the influence of the microflora on the distribution of endocrine cells and on the release of gastrointestinal peptides. METHODS: A quantitative morphological study using stereological methods was performed in gastrointestinal sections of conventional and germ-free rats. Tissue and plasma concentrations of peptides were measured. RESULTS: The total volumes of gastrin- and serotonin-immunoreactive cells were significantly increased in the gastric mucosa of germfree rats (P < 0.05), as well as the total volumes of serotonin- and motilin-immunoreactive cells in the ileum (P < 0.05) and serotonin-immunoreactive cells in the colonic mucosa (P < 0.05). The tissue concentration of somatostatin was significantly higher in the jejunum (P < 0.05) and lower in the ileum of germfree rats than in controls (P < 0.05). Plasma glucagon was significantly increased in germfree rats (P < 0.05). The total volume of the fundic mucosa was enlarged in germfree rats (P < 0.05), whereas the total volume, the mucosal thickness, and the number of crypt cells of the colonic mucosa were significantly reduced in these rats compared with controls (P < 0.05). CONCLUSIONS: Our findings suggest that the intraluminal microflora influences the release of biologically active peptides and that it participates in the regulation of gastrointestinal endocrine cells and the epithelial structure.

Animals↗
PubMed1994

Differential effects of sulfhydryl reagents on saxitoxin and tetrodotoxin block of voltage-dependent Na channels.

We have probed a cysteine residue that confers resistance to tetrodotoxin (TTX) block in heart Na channels, with membrane-impermeant, cysteine-specific, methanethiosulfonate (MTS) analogs. Covalent addition of a positively charged group to the cysteinyl sulfhydryl reduced pore conductance by 87%. The effect was selectively prevented by treatment with TTX, but not saxitoxin (STX). Addition of a negatively charged group selectively inhibited STX block without affecting TTX block. These results agree with models that place an exposed cysteinyl sulfhydryl in the TTX site adjacent to the mouth of the pore, but do not support the contention that STX and TTX are interchangeable. The surprising differences between the two toxins are consistent with the hypothesis that the toxin-receptor complex can assume different conformations when STX or TTX bound.

Animals↗
PubMed1994

Existence of a novel hemagglutinin having no protease activity in Vibrio mimicus.

The protease elaborated by Vibrio mimicus is known to possess hemagglutinating ability to chicken erythrocytes, the well-known HA/protease. A non-protease hemagglutinin (HA) with strong agglutinating ability towards rabbit erythrocytes was obtained from 32 hr culture supernatant of a pathogenic environmental strain of V. mimicus. This HA (V. mimicus HA: VMHA) appeared stable at relatively higher temperature and agglutinated the erythrocytes from rabbit, guinea pig and mouse but not the erythrocytes from chicken, bovine, horse and sheep. Simple sugars, metal ions and chelating agents failed to inhibit the activity of VMHA. The activity of VMHA was found to be sensitive to digestion by proteolytic enzymes including HA/protease. These results provide evidence for the existence of novel HA other than HA/protease in V. mimicus.

Animals↗
PubMed1994

Differential cell kinetics in the ileum and colon of germfree rats.

Our aim was to study the cell kinetics and epithelial structure in the ileum and colon of conventional and germfree AGUS rats by means of a classic stathmokinetic technique. A slight hyperplasia was observed in the villi of germfree animals (p < 0.05), associated with a comparatively short cell cycle time. The crypt cell production rate was reduced in the colon of germfree rats (p < 0.05), and their crypts contained fewer cells than those of conventional animals (p < 0.05). It is concluded that intraluminal bacteria influence cell proliferation in the colon. The absence of microflora prolongs the cell cycle time and reduces the proliferative activity in the colonic crypts, which contributes to a steady state that is different from that of conventional animals.

Animals↗
PubMed1994

Abnormal colonic microbial function in patients with rheumatoid arthritis.

The aim of this study was to examine the microflora-associated characteristics (MACs) of faecal samples of patients with rheumatoid arthritis (RA) and to evaluate the actions of sulphasalazine (SASP) on these MACs. The conversion of cholesterol to coprostanol, the production of urobilinogen, the degradation of faecal tryptic activity (FTA) and of beta-aspartylglycine were measured in faecal samples from 19 patients treated with SASP and 21 patients not treated with this medication. A control group of 21 healthy subjects was sex- and age-matched with the untreated patients. The conversion of cholesterol to coprostanol showed a bimodal distribution. The frequency of high converters in patients without SASP treatment was higher than in healthy subjects (p < 0.05). Treatment with SASP markedly increased the FTA and reduced the urobilinogen values, as compared to the untreated patients (p < 0.05). Beta-aspartylglycine was not found in any faecal samples. The results indicate that patients with RA have an abnormal formation of coprostanol, which is ascribed to alterations in the function of the Eubacteria species. In patients with RA, SASP treatment induces disturbances in the metabolism of the microflora.

Aged↗
PubMed1994

Anodic voltammetry of norgaman at rotating disc platinum and gold electrodes.

Norgaman has been examined by anodic rotating disc electrode voltammetry in buffered media over the range of pH from 0-11.5. The best medium is 0.1 mol 1(-1) sulphuric acid in which the anodic wave is well defined at lower rotation speeds. The compound does not show obedience to the Levich relationship at platinum and gold electrodes. Rapid determination of the compound is not possible due to the adsorption of the oxidation product. Electrode mechanism for the reaction has been elucidated.

Journal Article↗
PubMed1993

Synthesis and antiviral activity of 2'-substituted 9-[2-(phosphonomethoxy)ethyl]guanine analogues.

A series of 2'-substituted derivatives of 9-[2-(phosphonomethoxy)ethyl]guanine (PMEG, 1) have been synthesized and evaluated in vitro for anti-human immunodeficiency virus (HIV) activity in the XTT assay and for anti-herpes activity in the plaque reduction assay. It has been observed that the anti-HIV activity of these derivatives depends on the size and the nature of the substituent as well as the chirality at the 2'-position of PMEG. In addition, these compounds generally demonstrated greater activity against HIV than herpes viruses. The most interesting analogues which emerged from these studies are (R)-2'-(azidomethyl)-PMEG [(R)-5] and (R)-2'-vinyl-PMEG [(R)-11]. The former showed anti-HIV activity with an IC50 of 5 microM and a cytotoxicity (CC50) greater than 1.4 mM in CEM cells. The latter has an IC50 of 13 microM for anti-HIV activity and a CC50 of greater than 1.6 mM. Furthermore, we have demonstrated that replacement of the guanine base of these 2'-substituted PMEG analogues with cytosine drastically reduces anti-HIV and anti-herpes activity.

Antineoplastic Agents↗
PubMed1993

Mitral regurgitation following first-time acute myocardial infarction--early and late findings by Doppler echocardiography.

A total of 61 patients with first-time mild to moderate acute myocardial infarction and no reinfarction within the following 2 months were studied prospectively by Doppler echocardiography before hospital discharge and after 2 months to evaluate the prevalence of mitral regurgitation. Twenty-one age-matched healthy subjects served as controls. At baseline, the prevalence of Doppler-recorded mitral regurgitation was 74% and 29% in patients and controls, respectively. In the patients, the regurgitant flow measured by color flow Doppler was 1.04 cm2 (range 0.2-8 cm2) and occupied 7.5% (range 2-45%) of the left atrial area. Corresponding figures for controls were 0.35 cm2 (0.1-0.6) and 2.4% (0.7-4.5), respectively. On continuous wave Doppler, most patients (33/45) had Doppler signals similar to those of healthy controls. The prevalence of mitral regurgitation was about the same in anterior and inferior infarction (75 and 72% respectively). In the patients, the prevalence was similar after 2 months (79%) with minor changes in the Doppler characteristics of the regurgitation (regurgitant flow 1.12 cm2 and occupying 8.1% of left atrial area). The study demonstrates that in a group of patients with first-time mild to moderate myocardial infarction the prevalence of Doppler-recorded mitral regurgitation is high and mild in severity in the majority of the cases. The changes remain almost similar even after 2 months.

Acute Disease↗
PubMed1993

Substituted naphthalenones as a new structural class of HIV-1 reverse transcriptase inhibitors.

A novel substituted naphthalenone (TGG-II-23A) has been found that inhibits HIV-1 infection of CEM-SS cells at concentrations that are not cytotoxic. Time of addition experiments indicate that TGG-II-23A functions at a stage of the HIV-1 life cycle at or near reverse transcription. Cell free assays confirmed that TGG-II-23A inhibits HIV-1 reverse transcriptase. Similar to other non-nucleoside inhibitors, TGG-II-23A was specific for HIV-1 and failed to inhibit the replication of HIV-2. The binding site of TGG-II-23A appears to be in close proximity to that of the TIBO-like inhibitors, since a TIBO-resistant HIV-1 was also resistant to TGG-II-23A treatment. TGG-II-23A is a mixed non-competitive inhibitor that exhibits the same template:primer selectivity as other non-nucleoside inhibitors. TGG-II-23A therefore represents a new structural entry into the TIBO/Nevirapine class of inhibitors of HIV-1 reverse transcriptase.

Antiviral Agents↗