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Biomedical subjects

M Ali

Publications and source records attributed to M Ali.

At least 37 records · Page 2Linked to original sources
PubMed1999

Formation of 14,15-hepoxilins of the A(3) and B(3) series through a 15-lipoxygenase and hydroperoxide isomerase present in garlic roots.

We report herein for the first time the formation by freshly grown garlic roots and the structural characterization of 14,15-epoxide positional analogs of the hepoxilins formed via the 15-lipoxygenase-induced oxygenation of arachidonic acid. These compounds are formed through the combined actions of a 15(S)-lipoxygenase and a hydroperoxyeicosatetraenoic acid (HPETE) isomerase. The compounds were formed when either arachidonic acid or 15-HPETE were used as substrates. Both the "A"-type and the "B"-type products are formed although the B-type compounds are formed in greater relative quantities. Chiral phase high performance liquid chromatography analysis confirmed the formation of hepoxilins from 15(S)- but not 15(R)-HPETE, indicating high stereoselectivity of the isomerase. Additionally, the lipoxygenase was of the 15(S)-type as only 15(S)-hydroxyeicosatetraenoic acid was formed when arachidonic acid was used as substrate. The structures of the products were confirmed by gas chromatography-mass spectrometry of the methyl ester trimethylsilyl ether derivatives as well as after characteristic epoxide ring opening catalytically with hydrogen leading to dihydroxy products. That 15(S)-lipoxygenase activity is of functional importance in garlic was shown by the inhibition of root growth by BW 755C, a dual cyclooxygenase/lipoxygenase inhibitor and nordihydroguaiaretic acid, a lipoxygenase inhibitor. Additional biological studies were carried out with the purified intact 14(S), 15(S)-hepoxilins, which were investigated for hepoxilin-like actions in causing the release of intracellular calcium in human neutrophils. The 14,15-hepoxilins dose-dependently caused a rise in cytosolic calcium, but their actions were 5-10-fold less active than 11(S), 12(S)-hepoxilins derived from 12(S)-HPETE. These studies provide evidence that 15(S)-lipoxygenase is functionally important to normal root growth and that HPETE isomerization into the hepoxilin-like structure may be ubiquitous; the hepoxilin-evoked release of calcium in human neutrophils, which is receptor-mediated, is sensitive to the location within the molecule of the hydroxyepoxide functionality.

8,11,14-Eicosatrienoic Acid↗
PubMed1999

Mortality in severely malnourished children with diarrhoea and use of a standardised management protocol.

BACKGROUND: Severely malnourished children have high mortality rates. Death commonly occurs during the first 48 h after hospital admission, and has been attributed to faulty case-management. We developed a standardised protocol for acute-phase treatment of children with severe malnutrition and diarrhoea, with the aim of reducing mortality. METHODS: We compared severely malnourished children with diarrhoea aged 0-5 years managed by non-protocol conventional treatment, and those treated by our standardised protocol that included slow rehydration with an emphasis on oral rehydration. The standardised-protocol group included children admitted to the ICDDR,B Hospital, Dhaka between Jan 1, 1997, and June 30, 1997, while those admitted between Jan 1, 1996, and June 30, 1996, before the protocol was implemented, were the non-protocol group. FINDINGS: Characteristics on admission of children on standardised protocol (n=334) and non-protocol children (n=293) were similar except that more children on standardised protocol had oedema, acidosis, and Vibrio cholerae isolated from stools. 199 (59.9%) of children on standardised protocol were successfully rehydrated with oral rehydration solution, compared with 85 (29%) in the non-protocol group (p<0.0001). Use of expensive antibiotics was less frequent in children on standardised protocol than in the other group (p<0.0001). Children on standardised protocol had fewer episodes of hypoglycaemia than non-protocol children (15 vs 30, p=0.005). 49 (17%) of children on non-protocol treatment died, compared with 30 (9%) children on standardised protocol (odds ratio for mortality, 0.49, 95% CI 0.3-0.8, p=0.003). INTERPRETATION: Compared with non-protocol management, our standardised protocol resulted in fewer episodes of hypoglycaemia, less need for intravenous fluids, and a 47% reduction in mortality. This standardised protocol should be considered in all children with diarrhoea and severe malnutrition.

Anti-Bacterial Agents↗
PubMed1999

Alteration of substrate specificity by a naturally-occurring aldolase B mutation (Ala337-->Val) in fructose intolerance.

A molecular analysis of human aldolase B genes in two newborn infants and a 4-year-old child with hereditary fructose intolerance, the offspring of a consanguineous union, has identified the novel mutation Ala337-->Val in homozygous form. This mutation was also detected independently in two other affected individuals who were compound heterozygotes for the prevalent aldolase B allele, Ala149-->Pro, indicating that the mutation causes aldolase B deficiency. To test for the effect of the mutation, catalytically active wild-type human aldolase B and the Val337 variant enzyme were expressed in Escherichia coli. The specific activities of the wild-type recombinant enzyme were 4.8 units/mg and 4.5 units/mg towards fructose 1,6-bisphosphate (FBP) and fructose 1-phosphate (F-1-P) as substrates with Michaelis constants of 4 microM and 2.4 mM respectively. The specific activities of purified tetrameric Val337 aldolase B, which affects an invariant residue in the C-terminal region, were 4.2 units/mg and 2.6 units/mg towards FBP and F-1-P as substrates respectively; the corresponding Michaelis constants were 22 microM and 24 mM. The FBP-to-F-1-P substrate activity ratios were 0.98 and 1.63 for wild-type and Val337 variant enzymes respectively. The Val337 mutant aldolase had an increased susceptibility to proteolytic cleavage in E. coli and rapidly lost activity on storage. Comparative CD determinations showed that the Val337 protein had a distinct thermal denaturation profile with markedly decreased enthalpy, indicating that the mutant protein is partly unfolded. The undegraded mutant had preferentially decreased affinity and activity towards its specific F-1-P substrate and maintained appreciable activity towards FBP. In contrast, fluorescence studies of the mutant showed an increased binding affinity for products of the aldolase reaction, indicating a role for the C-terminus in mediating product release. These findings in a rare but widespread naturally occurring mutant implicate the C-terminus in the activity of human aldolase B towards its specific substrates and demonstrate its role in maintaining the overall stability of the enzyme tetramer.

Amino Acid Substitution↗
PubMed1999

Vascular volumes and hematology in male and female runners and cyclists.

To examine the hypothesis that foot-strike hemolysis alters vascular volumes and selected hematological properties is trained athletes, we have measured total blood volume (TBV), red cell volume (RCV) and plasma volume (PV) in cyclists (n = 21) and runners (n = 17) and compared them to those of untrained controls (n = 20). TBV (ml x kg(-1)) was calculated as the sum of RCV (ml x kg(-1)) and PV (ml x kg(-1)) obtained using 51Cr and 125I-labelled albumin, respectively. Hematological assessment was carried out using a Coulter counter. Peak aerobic power (VO2peak) was measured during progressive exercise to fatigue using both cycle and treadmill ergometry. RCV was 15% higher (P < 0.05) in male cyclists [35.4 (1.0), mean (SE); n = 12] and runners [35.3 (0.98); n = 9] compared to the controls [30.7 (0.92); n = 12]. Similar differences existed between the female cyclists [28.2 (2.1); n = 9] and runners [28.4 (1.0); n = 8] compared to the untrained controls [24.9 (1.4); n = 8]. For the male athletes, PV was between 19% (cyclists) and 28% (runners) higher (P < 0.05) in the trained athletes compared to the untrained controls. The differences in PV between the female groups were not significant. Although the males had a higher (P < 0.05) TBV, RCV and PV than the females, no differences between cyclists and runners were found for either gender. Mean cell volume was not different between the athletic groups. VO2peak (ml x kg(-1) x min(-1)) was higher (P < 0.05) in both male [68.4 (1.5)] and female [54.8 (2.1)] runners when compared to the untrained males [47.1 (1.0)] and females [40.5 (2.1)]. Although differences existed between the genders in VO2peak for both cyclists and runners, no differences were found between the athletic groups within a gender. Since the vascular volumes were not different between cyclists and runners for either the males or females, foot-strike hemolysis would not appear to have an effect on that parameter. The significant correlations (P < 0.05) found between VO2peak and RCV (r = 0.64 and 0.64) and TBV (r = 0.82 and 0.63) for the males and females, respectively, suggests a role for the vascular system in realizing a high aerobic power.

Adult↗
PubMed1999

Button battery ingestion: hazards of esophageal impaction.

Ingestion of button batteries has been seen with increasing frequency over the past decade. In a small number of reported cases, their impaction in the esophagus has led to serious, sometimes fatal, complications. The management of these cases has varied from expectant, supportive therapy to early surgical intervention. The authors report 2 pediatric patients in whom esophageal perforation developed after impaction of a disc battery. Both were treated conservatively with successful outcomes.

Caustics↗
PubMed1999

Respiratory distress in a child caused by lipoma of the esophagus.

A 6-year-old girl with a 2-year history of respiratory distress is described in this report. On investigation, a mass occupying the proximal half of the esophageal lumen, which was causing compression of the mediastinum, was found. It was removed surgically by a thoracic approach. On histological examination it was confirmed to be a lipoma of the esophagus. The child had an uneventful postoperative course. English-language literature on lipoma of the esophagus is reviewed briefly.

Child↗
PubMed1999

Role of GABA-A receptor in the preoptic area in the regulation of sleep-wakefulness and rapid eye movement sleep.

The role of GABA in medial preoptico-anterior hypothalamic area in the regulation of spontaneous sleep-wakefulness and rapid eye movement sleep was investigated in this study. Local microinjection of picrotoxin, a GABA-A antagonist, into this area increased quiet wakefulness but significantly reduced deep sleep and rapid eye movement sleep. Both the frequency of generation and duration per episode of the latter were significantly reduced. It is concluded that GABA-ergic neurotransmission in the medial preoptic area is spontaneously active in modulating the hypnogenic function including rapid eye movement sleep and the action is mediated by GABA-A receptor.

Animals↗
PubMed1999

The antihypertensive effect of garlic (Allium sativum) in the rat two-kidney--one-clip Goldblatt model.

A study was designed to elucidate the antihypertensive effect of garlic in the two-kidney--one-clip (2K-1C) Goldblatt model. Since the hypertension in this model depends largely on the increasing concentrations of vasopressor agents (prostaglandins and angiotensin II) there is a strong indication that reducing these factors could contribute in controlling the pathological rise in blood pressure. In this study, single or multiple doses of 0.5 ml of aqueous extract of garlic were given orally to 2K-1C rats. The data shows that the single dose of garlic used had a maximum antihypertensive effect 2-6 h after administration. The residual effect of this single dose continued for up to 24 h. The multiple dose of garlic appeared to be effective in restraining the expected rise in blood pressure that normally occurs in 2K-1C rats. Switching multiple-dose treatments halfway through the experiment further strengthened the findings. The study suggests that garlic does have an effective antihypertensive ability, and may be used as a supplementary and natural remedy in cases of unilateral renovascular hypertension.

Animals↗
PubMed1999

The effects of parathyroidectomy on nutritional and biochemical status of hemodialysis patients with severe secondary hyperparathyroidism.

The nutritional and biochemical parameters of 15 chronic hemodialysis (HD) patients with severe secondary hyperparathyroidism who had undergone total parathyroidectomy (PTX), with a forearm implant, were retrospectively studied at 1, 3, 6, and 12 months pre- and post-PTX. The concentrations of serum calcium and phosphorous significantly decreased in the first 6 months post-PTX. The concentration of blood urea nitrogen significantly increased at 6 and 12 months post-PTX. In contrast with control chronic HD patients who had no weight gain after nonparathyroid surgery, there was a progressive weight gain leading to a significantly higher dry weight at 12 months post-PTX. There was no significant change in serum potassium, albumin, cholesterol, transferrin, bicarbonate, hematocrit, normalized protein catabolic rate (nPCR), or erythropoietin dose at any time point post-PTX. The biochemical parameters of the 8 patients who had more than 5% weight gain, during 12 months post-PTX, were not statistically different from the remaining 7 cases who had weight gain less than 5% (or had lost weight) in the same time period. The same was true for 4 patients with weight gain of more than 10% versus the latter group. In conclusion, HD patients with severe secondary hyperparathyroidism are prone to progressive weight gain post-PTX, which reaches significance by the twelfth month. In 53% of the patients, the weight gain is more than 5% above the baseline. The nutritional and biochemical parameters pre-PTX were not helpful in distinguishing those who developed significant weight gain post-PTX.

Adult↗
PubMed1999

Determinants of contraceptive discontinuation in six developing countries.

This analysis investigates the determinants of contraceptive discontinuation in six developing countries, using data from Phase I surveys of the DHS programme. Cumulative probabilities of discontinuation at 24 months for reasons other than the desire for another child were examined. By this time, typically about 40% of couples have stopped use and most are subsequently at risk of an unwanted conception. Discontinuation of IUD use was found to be less common than for other methods, partly perhaps because cessation of use requires a deliberate decision to have the device removed. The most important results are negative ones. Neither the schooling of couples nor their type of residence exerted appreciable influence on discontinuation. The policy and programme implications are discussed. Prior use of a method, fertility preferences and the related demographic factors of age and family size emerged as pervasive predictors of discontinuation.

Adolescent↗
PubMed1999

CFTR antisense phosphorothioate oligodeoxynucleotides (S-ODns) induce tracheo-bronchial mucin (TBM) mRNA expression in human airway mucosa.

Mucus hypersecretion is a critical component of cystic fibrosis (CF) pathogenesis. The effects of dysfunction of the cystic fibrosis transmembrane regulator (CFTR) on mucin expression were examined using the tracheo-bronchial mucin (TBM) gene as an indicator. TBM mRNA expression was assessed in a human bronchial epithelial cell line (HBE1) and human nasal mucosal explants in vitro. Antisense phosphorothioate oligodeoxynucleotides (S-ODN) to TBM suppressed baseline expression of TBM mRNA in both systems, but had no effect on glyceraldehyde phosphate dehydrogenase mRNA (GAPDH) expression. Sense and missense (multiple scrambled control oligonucleotides) S-ODNs had no effect. 8Br-cAMP and PGE1 significantly elevated TBM mRNA expression. These increases were also specifically inhibited by the antisense S-ODNs. In order to induce a CF-like state, S-ODN to CFTR were added to explants. Antisense CFTR S-ODNs were anticipated to reduce the expression of cellular CFTR protein, and the level of CFTR function. Antisense, but not sense or missense, CFTR S-ODN significantly increased TBM mRNA expression. These data suggest that mucin hypersecretion in CF may be a direct consequence of CFTR dysfunction; the specific mechanism through which this effect is mediated is not known.

Cells, Cultured↗
PubMed1999

Altered expression of the Na+/H+ exchanger isoform-3 in experimental colitis: effect of garlic.

The sodium-hydrogen exchanger isoform, NHE-3 is essential for the absorption of sodium and water from intestine. Whether this protein plays any role in inflammatory bowel disease is less understood. To address this issue, NHE-3 mRNA and protein levels were estimated in the terminal ileum and colon of the rats having colitis induced with trinitrobenzenesulphonic acid (TNBS). The effect of garlic (Allium sativum) was also evaluated on the expression of NHE-3. The animals were treated with garlic extract intraperitoneally starting 2 h before the TNBS administration until day 4 post-TNBS administration and were sacrificed on day 5. In control animals, the levels of NHE-3 in colon was higher than the ileum. As a result of colitis, the levels of NHE-3 protein and mRNA increased both in the colon and terminal ileum. Garlic treatment of the colitic animals resulted in a selective suppression of NHE-3 in the terminal ileum. Colitis caused an induction of the myeloperoxidase activity, the marker of inflammation in the colon but not in the ileum. These findings suggest that induction of NHE-3 is not primarily due to inflammation. Selective suppression of this protein in ileum by garlic may cause loss of sodium chloride and water during colitis.

Animals↗
PubMed1999

Effect of raw versus boiled aqueous extract of garlic and onion on platelet aggregation.

The effects of aqueous extracts of raw and boiled garlic and onions were studied in vitro on the collagen-induced platelet aggregation using rabbit and human platelet-rich plasma. A dose dependant inhibition of rabbit platelet aggregation was observed with garlic. Onion also showed dose-dependent inhibitory effects on the collagen-induced platelet aggregation but this inhibition was of a lesser magnitude compared to garlic when related to dose. The concentration required for 50% inhibition of the platelet aggregation for garlic was calculated to be approximately 6.6 mg ml(-1) plasma, whereas the concentration for onion was 90 mg ml(-1) plasma. Boiled garlic and onion extracts showed a reduced inhibitory effect on platelet aggregation. Garlic but not onion significantly inhibits human platelet aggregation in a dose-dependent fashion. The potency of garlic in inhibiting the collagen-induced platelet aggregation is approximately similar to that of rabbit platelets (8.8 mg ml(-1) produced 50% inhibition of platelet aggregation). The results of this study show that garlic is about 13 times more potent than onion in inhibiting platelet aggregation and suggest that garlic and onion could be more potent inhibitors of blood platelet aggregation if consumed in raw than in cooked or boiled form.

Animals↗
PubMed1999

Hypotensive, hypoglycaemic and toxicological studies on the flavonol C-glycoside shamimin from Bombax ceiba.

Shamimin, a C-flavonol glucoside from Bombax ceiba leaves showed significant potency as a hypotensive agent at the doses of 15 mg/kg, 3 mg/kg, 1 mg/kg and significant hypoglycaemic activity at 500 mg/kg in Sprague-Dawley rats. Further studies revealed that it did not cause any mortality in mice at the dose of 1 g/kg but in rats 500 mg/kg is a lethal dose. Aqueous and methanolic extracts of Bombax ceiba leaves and one of its fractions were also subjected to pharmacological and toxicological screening.

Animals↗
PubMed1999

Shamimin: a new flavonol C-glycoside from leaves of Bombax ceiba.

Shamimin a new flavonol C-glycoside has been isolated as a pale yellow powder from the ethanolic extract of fresh, undried leaves of Bombax ceiba. Its structure has been elucidated as 2-(2,4,5-trihydroxyphenyl)-3,5,7-trihydroxy-6-C- glucopyranosyloxy-4H-1-benzopyran-4-one through extensive spectroscopic methods (IR, mass, 1H- and 13C-NMR), and 2D-NMR experiments. Shamimin showed antimicrobial activity against a few bacteria and fungi.

Anti-Bacterial Agents↗
PubMed1999

Measurement of serum N-acetyl beta glucosaminidase activity in patients with breast cancer.

N-acetyl-beta-glucosaminidase (NAG) activity measured in sera from 129 breast cancer patients was elevated (mean 18.2 units/l) compared with that in sera from 28 healthy women (11.6 units/l) (p=0.001). There was a weak correlation between NAG activity and carcinoembryonic antigen (CEA) and CA-153, but no relationship to age, menopausal status, node status, stage, histology of tumour or to steroid receptors. NAG, CEA and CA-153 were measured in periodic follow-up samples taken after surgery (up to 26 months) from 17 patients. NAG activity fluctuated within a narrow range, unlike CEA and CA-153. In 70% of cases the pattern was similar to at least one of the other markers, and was generally maintained at a higher level in patients who suffered relapse compared with those who remained disease-free up to the last follow-up, but was not significantly altered before relapse. The measurement of NAG activity is unlikely to be of value in predicting time or occurrence of relapse or of clinical utility in post-surgical therapy. Increased appearance in serum may aid metastasis by degrading the extracellular matrix and it may be better investigated as a predictor of progression from in situ to invasive and metastatic cancer.

Acetylglucosaminidase↗
PubMed1999

Immunoradiometric measurement of pS2 in breast cancer--correlation with steroid receptors and plasminogen activators.

pS2 was measured by radioimmunometric assay in tumour extracts from 197 breast cancer patients. Values ranged from 0 to 50 ng/mg protein (mean 9.6 and median 3 ng/mg). We found no correlation with age, menopausal status, nodal metastases, disease stage or tumour histology. There was, however, a linear relationship with both ER (p < 0.0001) (particularly nuclear ER) and PR (p < 0.0001) expression determined by enzyme immunoassay (ELISA), as well as a good correlation when high and low expressors were stratified on the basis of combined ER/PR expression using consensus cut-off points. Only 15% of ER - ve/PR - ve patients were classified as pS2 + ve compared with 83% of those who were ER + ve/PR + ve. pS2 was also directly correlated with high expression of tPA and inversely with uPA. Comparison with previous studies showed that the current ELISA method produced consistent results, in contrast to other methods, particularly those based on immunohistochemical detection. The close relationship between pS2 and both steroid receptors suggests that pS2 may be important in terms of defining hormone-responsive patients who are likely to benefit from endocrine therapy.

Breast Neoplasms↗