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Biomedical subjects

M Siddiqi

Publications and source records attributed to M Siddiqi.

At least 19 recordsLinked to original sources
PubMed2005

Induction of apoptosis in human leukemia cells by black tea and its polyphenol theaflavin.

Treatment of human leukemic cell lines HL-60 and K-562 with extracts of green and black tea and their polyphenols epigallocatechin gallate and theaflavins, respectively, showed a dose dependent inhibition of growth as a result of cytotoxicity and suppression of cell proliferation. Based on the IC50 values obtained from cytotoxicity data it was clearly evident that black tea was as efficient as green tea. Analysis of polyphenol contents of tea extracts revealed that not only epigallocatechin gallate, which is a predominant polyphenol of green tea, but also theaflavin that is abundantly present in black tea affords significant chemotherapeutic action by imparting cytotoxicity to human leukemic cells. Electrophoretic analysis of fragmented DNA from treated cells displayed characteristic ladder pattern. Flow cytometric analysis revealed the dose dependent increase in sub-G1 peak. These criteria confirmed that cytotoxic activity of green and black tea was due to induction of apoptosis. Such induction was found to be mediated through activation of caspases 3 and 8, particularly caspase 3 and by altering apoptosis related genes as evident by down-regulation of Bcl-2 and up-regulation of Bax proteins.

Antioxidants↗
PubMed2001

Relationship between oxidative burst activity and CD11b expression in neutrophils and monocytes from healthy individuals: effects of race and gender.

Oxidative burst activity and the expression of adhesion molecules have been used as indicators of leukocyte activation status. The aim of the study was to delineate the relationship of oxidative burst activity and the expression of adhesion molecules in neutrophils and monocytes from a pool of healthy volunteers (n = 96). We also tested the potential role of gender and a racial background in the individual response differences. Basal and phorbol myristate acetate (PMA)-stimulated oxidative burst and CD11b expression were determined using dihydrorhodamine 123 and phycoerythrin (PE)-conjugated anti-CD11b monoclonal antibodies. PMA markedly increased CD11b expression and cellular oxidant content in neutrophils and monocytes in all samples. However, the responses showed considerable variability among individuals. A positive correlation was observed between the responsiveness of neutrophils and monocytes in their basal or PMA-stimulated CD11b expressions and PMA-stimulated oxidative burst activities. In contrast, no correlation was found between the level of adhesion molecule expression and cellular oxidant content in monocytes or neutrophils either under basal or under PMA-stimulated conditions. The reactivity of oxidative burst (i.e., PMA-stimulated over basal) was significantly lower in neutrophils from African American males compared with cells from African American females, white females, or white males. In contrast, reactivity of monocytes was significantly elevated in white males compared with all other groups. These findings indicate that leukocytes with a relatively high degree of adhesion molecule expression may display an average or decreased oxidative burst activity, and vice versa. Our findings also indicate that ethnic background may influence the oxidative burst activity in neutrophils and monocytes. This needs consideration in clinical studies utilizing healthy volunteers with mixed gender and ethnic backgrounds.

Black People↗
PubMed2001

Increased incidence of sepsis and altered monocyte functions in severely injured type A- glucose-6-phosphate dehydrogenase-deficient African American trauma patients.

OBJECTIVE: To determine whether trauma patients with the common, type A- glucose-6-phosphate dehydrogenase (G6PD) deficiency have an aggravated inflammatory response, increased incidence of septic complications, and/or more profound alterations in leukocyte functions compared with nondeficient trauma patients. SETTINGS: Intensive and surgical care units of a trauma center and flow cytometry and experimental laboratories at a teaching university hospital. DESIGN: Prospective cohort clinical study with measurements on days 2 and 5 postinjury. Monocyte and neutrophil oxidant content, apoptosis, and CD11b expression and plasma cytokine levels were compared between G6PD-deficient and nondeficient patients. PATIENTS: A total of 467 male African American trauma patients were screened for the deficiency. Forty-four type A-202/376 G6PD-deficient patients were identified and enrolled in the study; 43 nondeficient patients were also enrolled and were matched by age, clinical criteria of injury severity, and type of trauma. MAIN RESULTS: After severe injury (Injury Severity Score, > or =16), 50% of the deficient and 6.2% of nondeficient patients developed sepsis with positive bacterial blood cultures. In deficient patients, the frequency of bronchial (75%) and wound infections (25%) was also increased compared with nondeficient patients (32% and 0%). The durations of systemic inflammatory response syndrome, Sepsis Syndrome, and days on antibiotics were three times longer in deficient than in nondeficient individuals. However, adult respiratory distress syndrome occurred in 37% of both groups. Anemia was more severe in the deficient than nondeficient patients from day 10 posttrauma. On day 5, the peroxide content was doubled, apoptosis was decreased, and CD11b expression was increased in monocytes from deficient patients compared with cells from nondeficient patients. On day 5, the plasma interleukin (IL)-10 concentration was significantly lower in deficient than nondeficient patients, whereas tumor necrosis factor-alpha, IL-6, and IL-8 levels were similar. After moderate injuries (Injury Severity Score, 9-16), the deficiency was not associated with adverse clinical effects, and the trauma-induced changes in leukocyte function were similar in deficient and nondeficient patients. CONCLUSIONS: The common type A- G6PD deficiency predisposes septic complications and anemia in trauma patients after severe injuries as defined by an Injury Severity Score of > or =16. This adverse clinical course is accompanied by altered monocyte functions manifested as augmented oxidative stress, a decreased apoptotic response, increased cell adhesion properties, and a diminished IL-10 response.

Adult↗
PubMed2001

Using lot quality assurance sampling to improve immunization coverage in Bangladesh.

OBJECTIVE: To determine areas of low vaccination coverage in five cities in Bangladesh (Chittagong, Dhaka, Khulna, Rajshahi, and Syedpur). METHODS: Six studies using lot quality assurance sampling were conducted between 1995 and 1997 by Basic Support for Institutionalizing Child Survival and the Bangladesh National Expanded Programme on Immunization. FINDINGS: BCG vaccination coverage was acceptable in all lots studied; however, the proportion of lots rejected because coverage of measles vaccination was low ranged from 0% of lots in Syedpur to 12% in Chittagong and 20% in Dhaka's zones 7 and 8. The proportion of lots rejected because an inadequate number of children in the sample had been fully vaccinated varied from 11% in Syedpur to 30% in Dhaka. Additionally, analysis of aggregated, weighted immunization coverage showed that there was a high BCG vaccination coverage (the first administered vaccine) and a low measles vaccination coverage (the last administered vaccine) indicating a high drop-out rate, ranging from 14% in Syedpur to 36% in Dhaka's zone 8. CONCLUSION: In Bangladesh, where resources are limited, results from surveys using lot quality assurance sampling enabled managers of the National Expanded Programme on Immunization to identify areas with poor vaccination coverage. Those areas were targeted to receive focused interventions to improve coverage. Since this sampling method requires only a small sample size and was easy for staff to use, it is feasible for routine monitoring of vaccination coverage.

BCG Vaccine↗
PubMed1998

Caffeine-derived N-nitroso compounds. V. Carcinogenicity of mononitrosocaffeidine and dinitrosocaffeidine in bd-ix rats.

Mononitrosocaffeidine (MNC) and dinitrosocaffeidine (DNC) are new N-nitroso compounds obtained from in vitro nitrosation of caffeidine, a hydrolysis product of caffeine present in a typically made and widely consumed tea from Kashmir (India), a high incidence area of esophageal and stomach cancer. The chemical synthesis, in vitro metabolic studies and mutagenicity of the compounds has been previously reported. DNC, a nitrosamide is highly mutagenic both with and without metabolic activation whereas MNC, like several other aromatic asymmetric nitrosamines, does not exhibit genotoxic or mutagenic properties. We now report the results of the first carcinogenicity experiments on chronic oral administration of these compounds in BD-IX rats. The acute LD50 of MNC and DNC were about 1300 and 230 mg/kg b.w., respectively. Lung oedema and gastrointestinal haemorrhages were the first symptoms of intoxication observed after 2 days for both the compounds. All three dose groups of MNC treated rats showed localization of tumours in nasal cavity (93.9-100% of all malignant tumours). The tumours were histologically diagnosed as neuroepitheliomas of the olfactory epithelium (neuroblastoma of the bulbus olfactorii) and squamous cell carcinoma of the nasal cavity in the ratio of 3:1. No tumours of the nasal cavity were observed in the untreated controls. DNC, in contrast, induced squamous cell carcinoma of forestomach in 100% animals at low and high doses, of which nearly half the tumours metastasized predominantly into the peritoneum. No forestomach tumours were seen in the untreated controls. The data presented here clearly show the potential for induction of malignant tumours and distinct organ-specificity by MNC and DNC in rats, and support the postulate that a chronic exposure to these compounds may provide a carcinogenic risk for high incidence of gastrointestinal cancers in Kashmir.

Administration, Oral↗
PubMed1994

Identification of nitrophenols as nitrosation products from capsaicin and red chillies.

The in vitro nitrosation of sun-dried red chillies (Capsicum annuum) and of its constituents capsaicin and dihydrocapsaicin was studied. The nitrophenols 4-nitroguaiacol, 4,6-dinitroguaiacol, nitrocapsaicin and nitrodihydrocapsaicin were detected as final products, whereas no formation of nitrosamides was observed though this is expected from the amide precursors capsaicin and dihydrocapsaicin. The nitrosation occurs readily with remarkable yields of nitrophenols even at physiological pH and at nitrite concentrations which are within the range of those found in the human stomach. Due to their toxicity, nitrophenols need to be included in total risk assessment through potential endogenous nitrosation of foodstuffs.

Capsaicin↗
PubMed1994

Caffeine-derived N-nitroso compounds. IV: Kinetics of mononitrosocaffeidine demethylation by rat liver microsomes.

The study describes the kinetics of demethylation of mononitrosocaffeidine (MNC), a new asymmetric N-nitrosamine derived from caffeine. The demethylation of its precursor compound caffeidine was also studied. The results presented here suggest (a) that liver microsomes from fasted rats preferentially demethylate the N-methylnitrosamine group in MNC indicating the demethylation by cytochrome P450IIE1, (b) demethylation of MNC shows two apparent Km values, one of 117-166 microM responsible for the demethylation at the N-methylnitrosamino group of MNC, and the other Km of 1.84-2.26 mM for the remaining N-demethylations, (c) in contrast, caffeidine is a low affinity substrate for microsomal demethylation as indicated by a high Km of 14.3-16.3 mM, and (d) the demethylation at amino-N amino-N, and N-1 in both these compounds are mainly catalysed by P450 enzymes induced by Aroclor 1245 in rats.

Animals↗
PubMed1993

Caffeine-derived N-nitroso compounds. III: Mutagenicity in S. typhimurium and in vitro induction of DNA single-strand breaks in rat hepatocytes by mononitrosocaffeidine and dinitrosocaffeidine.

Mutagenesis in S. typhimurium and in vitro induction of DNA single-strand breaks in primary rat hepatocytes (DNA-SSB) have been investigated for two new N-nitroso compounds, mononitrosocaffeidine (MNC) and dinitrosocaffeidine (DNC). Mononitrosamidocaffeidine (MNAC) and tert.-(butyloxy)carbonyl-mononitrosamidocaffeidine (t-BOC-MNAC), both nitrosated derivatives of caffeidine with nitrosation at methylcarboxamide-N only, were also similarly studied. MNC, an asymmetric nitrosamine, failed to show mutagenicity in any of the tester strains used, and also did not induce DNA-SSB in rat hepatocytes. DNC, having both N-nitrosamide and N-nitrosamine groups in the molecule, showed direct mutagenicity in TA100, TA1535 and TA102. The mutagenic potential of the compound was found to increase on S9 activation. However, it was non-mutagenic in TA98 and TA1537. DNC also exhibited a high potential for inducing alkali-labile DNA-SSB in rat hepatocytes (70-78% C-T value) and was cytotoxic at concentrations over 0.1 mumole/ml. Both MNC and DNC were found to produce formaldehyde on S9 activation. MNAC was not mutagenic directly but showed weak mutagenicity on metabolic activation, whereas t-BOC-MNAC was mutagenic both with and without S9 activation in TA100, TA1535 and TA102. t-BOC-MNAC was more cytotoxic to hepatocytes than MNAC, though both caused DNA-SSB to the same extent (62% C-T value). On the basis of the presented data it is inferred that while DNC is a direct-acting mutagen in TA100, TA1535 and TA102 due to the presence of a reactive N-methylnitrosamido group, its mutagenic potential is greatly enhanced in the presence of S9 possibly due to the synergistic influence of an activated N-methylnitrosamino group in the molecule. Additionally, the study shows a qualitative consistency between Salmonella mutagenicity, genotoxicity in hepatocytes and the reactivity of the methyl group at the nitrosamido-N in nitrosated caffeidine compounds.

Animals↗
PubMed1992

Effect of dietary nitrate on endogenous nitrosation of piperazine in humans.

The effect of dietary nitrate on endogenous nitrosation of a therapeutic dose of piperazine has been described in five human volunteers who acted as their own controls. The urinary excretion of endogenously formed N-nitro-somonopiperazine (MNPz) ranged between 9.2 and 80.1 micrograms/24 h on a normal uncontrolled diet which increased from 25.7 to 163.7 micrograms/24 h when the diet was supplemented with 250 mg nitrate. The corresponding urinary nitrate was 63.0-122.7 mg/24 h and 119.2-322.0 mg/24 h, respectively. The dinitroso derivative of piperazine was detected only in trace amounts and no detectable increase in its excretion was observed during high nitrate exposure. The unchanged piperazine (range 294-784 mg/24 h) in urine showed a decrease under high nitrate regimen (range 185-399 mg/24 h).

Carcinogens↗
PubMed1992

Caffeine-derived N-nitroso compounds--I: Nitrosatable precursors from caffeine and their potential relevance in the etiology of oesophageal and gastric cancers in Kashmir, India.

Salted tea prepared in Kashmir by adding sodium bicarbonate shows high methylating activity (equivalent to 3 p.p.m. N-methylnitrosourea) upon in vitro nitrosation. Pure caffeine treated under conditions of the tea preparation formed caffeidine and caffeidine acid. We report here the formation of two new compounds, mononitrosocaffeidine, an asymmetric nitrosamine, and dinitrosocaffeidine, a N-nitrosamide, on in vitro nitrosation of caffeidine. Mononitrosocaffeidine is also found after nitrosation of the typical Kashmir tea. The nitrosation of caffeidine acid produced N,N'-dimethyl-parabanic acid, mononitrosocaffeidine and N,N'-dimethyl-N-nitrosourea. In view of the well-known structure-activity relationships of these N-nitroso compounds, their possible endogenous formation due to high consumption of salted tea may be a critical risk factor for the high occurrence of oesophageal and gastric cancers in Kashmir.

Bicarbonates↗
PubMed1992

Increased exposure to dietary amines and nitrate in a population at high risk of oesophageal and gastric cancer in Kashmir (India).

Analytical data on aliphatic amines and nitrate from the most commonly used fresh and sun-dried vegetables, red chillies and a widely consumed beverage, salted tea, are presented from a high risk area for oesophageal and gastric cancer in Kashmir. Exposure estimates for the adult population show that high consumption of boiled Brassica vegetables leads to a high nitrate intake of 237 mg/day. The frequent consumption of hot salted tea is shown to result in exceptionally high exposure to methylamine (1200 micrograms/day), ethylamine (14,320 micrograms/day), dimethylamine (150 micrograms/day) and diethylamine (400 micrograms/day). The indiscriminate use of red chillies in the area leads to exposure to dimethylamine (280 micrograms/day), pyrrolidine (517 micrograms/day) and methylbenzylamine (40 micrograms/day). This is to our knowledge the first report where a chronic exposure to methylbenzylamine has been shown in a population at high risk of oesophageal cancer.

Adult↗
PubMed1991

Tobacco-specific N-nitrosamines in tobacco and mainstream smoke of Indian cigarettes.

Different brands of Indian cigarettes were analysed, by gas chromatography-thermal energy analysis, for the presence of carcinogenic tobacco-specific N-nitrosamines (TSNA) in both tobacco and mainstream smoke. Preformed TSNA in cigarette tobacco ranged between 68 and 730 ng N-nitrosonornicotine (NNN)/cigarette, between 19 and 174 ng 4-(N-nitrosomethylamino)-1-(3-pyridyl)-1-butanone (NNK)/cigarette and between 98 and 519 ng N-nitrosoanabasine (NAB) together with N-nitrosoanatabine (NAT)/cigarette. The amounts of NNN, NNK and NAB/NAT in mainstream smoke were 11-156, 7-73 and 17-146 ng/cigarette, respectively.

Chromatography, Gas↗
PubMed1991

Endogenous formation of N-nitrosamines from piperazine and their urinary excretion following antihelmintic treatment with piperazine citrate.

Antihelmintic treatment with piperazine (1,4-diazacyclohexane) for microfilarie parasitism results in the endogenous formation of piperazine-derived N-nitrosamines. The urinary excretion of these N-nitrosamines was determined by biochemical monitoring of 14 patients receiving 2 g piperazine citrate. The urinary excretion (mean +/- SD) of N-mononitrosopiperazine (MNPz) was 27.0 +/- 26.7 micrograms/day (range 0.6-96.0 micrograms/day). Trace levels of 0.73 +/- 0.92 micrograms/day N,N'-dinitrosopiperazine (DNPz) (range ND-2.8 micrograms/day) were also found in 7 of 14 urine samples. N-Nitroso-3-hydroxypyrrolidine (NHPYR), a metabolite of both MNPz and DNPz, was detected in 11 of 14 urine samples at a mean concentration of 1.74 +/- 1.72 micrograms/day (range ND-5.7 micrograms/day) and traces of N-nitrosodiethanolamine in two samples at levels of 0.3 and less than 0.1 micrograms/day. The results show that biochemical monitoring of urinary NHPYR may be a good indicator of endogenous MNPz formation. While DNPz was also detected in urine, conclusive validation for its endogenous formation could not be provided because no evidence was found for the presence of its major metabolite, N-nitroso-(2-hydroxyethyl)glycine in urine.

Adult↗
PubMed1990

N-nitroso compounds and their precursors in Brassica oleracea.

In the present study, Brassica a dried green vegetable from Kashmir, which is a major constituent of the local diet, was analysed for nitrosatable aliphatic amines, N-nitrosamines prior to and after nitrosation) and alkylating activity due to N-nitrosamides following nitrosation. The cooked vegetable contained 11 micrograms/kg nitrosodimethylamine and 21 micrograms/kg nitrosopyrrolidine. Nitrosation under chemical conditions yielded 1200 micrograms/kg N-methylnitrosourea.

Brassica↗
PubMed1988

Occurrence of volatile N-nitrosamines in dried chillies.

Twenty samples of dried chillies, fresh chillies and chilli sauces have been analysed for the presence of volatile N-nitrosamines. Over 75% of both dried whole chillies and chilli powder samples analysed contained N-nitrosodimethylamine and N-nitrosopyrrolidine (NPYR) at concentrations of 0.66-16.5 micrograms/kg and 0.48-6.0 micrograms/kg, respectively. Fresh chillies and chilli sauces were not found to contain volatile N-nitrosamines.

Condiments↗