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Biomedical subjects

Z Iqbal

Publications and source records attributed to Z Iqbal.

At least 37 records · Page 2Linked to original sources
PubMed1997

Organochlorine pesticide residues in human blood in the population of Multan (Pakistan).

Organochlorine pesticide residues were monitored in samples of human blood (N=32), obtained from concerned volunteers suspecting oral, dermal, or inhalation exposure to Endosulfan and Heptachlor, either environmentally, or occupationally, either recently or in the recent past of Multan Division, (Pakistan) during 1995-96. The pesticide residues were extracted with n-hexane; detection and quantification was performed by gas chromatography (Shimadzu GC 14-A) with a 63Ni-Electron Capture Detector (ECD). Residues of Endosulfan were found higher as compared to Heptachlor in all samples. The highest concentration of Endosulfan residues in blood in the population of Multan and Mailsi regions was 90.29 g/kg and 82.14 g/kg, lowest as 58.13 g/kg and 60.13 g/kg while Heptachlor had highest level as 12.978 g/kg and 9.997 g/kg, minimum as 0.37 g/kg and 1.23 g/kg respectively.

Journal Article↗
PubMed1996

Front-line management of pulmonary tuberculosis: an analysis of tuberculosis and treatment practices in urban Sindh, Pakistan.

SETTING: Karachi and Hyderabad, Pakistan. OBJECTIVE: To describe the level and quality of tuberculosis (TB) case management by non-TB control program (TCP) physicians in urban Sindh, Pakistan. DESIGN: We interviewed 152 adults with pulmonary TB confirmed by Karachi's TB control program regarding the initial management of their TB symptoms before entering the TCP. We also surveyed 65 general practitioners (GPs) attending continuing education seminars with a multiple choice test to assess their management of suspected pulmonary TB. We compared both results to guidelines from the World Health Organization (WHO) and the International Union Against Tuberculosis and Lung Disease (IUATLD). RESULTS: Eighty percent (122/152) of patients first sought GPs. Only 14% of GPs performed any sputum test. At most, 17 (40%) of the 42 patients recalling their GP's treatment, received the recommended 4-drug regimen. However, 68% (45/65) of surveyed GPs chose correct treatment from a multiple choice format. But their initial laboratory investigations, follow-up, and treatment cessation criteria (9%, 9-31%, and 11% correct, respectively) demonstrated under-utilization of sputum tests and over-reliance on unhelpful tests. CONCLUSIONS: GPs first saw most of these TCP patients, but their weak management likely hinders TB control. A partnership between TB control programs and GPs could improve case management and hasten TB control.

Adolescent↗
PubMed1996

Linkage of scapuloperoneal spinal muscular atrophy to chromosome 12q24.1-q24.31.

Scapuloperoneal (SP) syndromes are heterogeneous neuromuscular disorders which are characterized by weakness in the distribution of shoulder girdle and peroneal muscles. SP syndromes can resemble facioscapulohumeral muscular dystrophy (FSH) due to scapular weakness or Charcot-Marie-Tooth disease (CMT) due to atrophy of peroneal muscles. Both neurogenic and myopathic SP syndromes have been described. Locus for the myopathic form of SP syndrome (scapuloperoneal muscular dystrophy, SPMD) has recently been assigned to chromosome 12q. We previously described a large New England kindred exhibiting an autosomal dominant neurogenic SP syndrome (scapuloperoneal spinal muscular atrophy, SPSMA). Disease expression was more severe and progressive in successive generations, which suggested genetic anticipation. We performed genetic linkage analysis of this family with microsatellite markers and excluded the loci for FSH, CMT, SPMD and SMA (spinal muscular atrophy) in our family. Linkage in our SPSMA family (lod score > 3) was established to seven microsatellite markers that map to chromosome 12q24.1-q24.31. The highest lod score with two-point linkage analysis was 6.67 (theta = 0.00) with marker D12S353. Multipoint analysis gave maximum lod scores of 7.38 between D12S354 and D12S79, and also 7.38 between D12S369 and NOS1 (neuronal nitric oxide synthase). The gene for SPSMA lies within the 19 cM interval between D12S338 and D12S366. This report establishes a locus for the neurogenic form of SP syndrome approximately 20 cM telomeric to the one described for the myopathic form of SP syndrome.

Chromosome Mapping↗
PubMed1995

Acute and chronic actions of ethanol on endogenous calmodulin content in synaptic plasma membranes from rat brain.

The present study was designed to demonstrate that endogenous calmodulin (CaM) content in synaptic plasma membranes (SPM) is altered by acute and chronic administration of ethanol and is a sequel to the kinetic characterization of ethanol inhibition of [125I]CaM binding to SPM reported in our previous study. In rats, an acute ethanol injection (2 g/kg, i.p.) rapidly reduced CaM content in SPM from cerebral cortex, whereas chronic ethanol treatment [6% (w/v) in a liquid diet for 3 weeks] led to an up-regulation of the CaM content. In both cases, the alteration of CaM content in SPM occurred in the EGTA-dissociable pool of CaM (77% of total membrane CaM); the EGTA-nondissociable pool (23% of total CaM) was not affected. In animals receiving chronic ethanol treatment, CaM content in SPM was not altered significantly by the acute ethanol dose that produced rapid reduction of CaM content in control animals, indicating that resistance to ethanol develops. This resistance to ethanol can be attributed to alterations of membrane properties. In control SPM, ethanol at 50 mM markedly accelerated the temperature-dependent dissociation of endogenous CaM, whereas in SPM from animals chronically treated with ethanol, significant acceleration of CaM dissociation required ethanol concentrations as high as 150-200 mM. These findings on SPM in vitro were consistent with the data on CaM content obtained in vivo. Since CaM mediates a variety of biochemical processes in synaptic membranes, we hypothesize that the effects of ethanol in altering the content of membrane-bound CaM may lead to a cascade of consequences in synaptic membrane function.

Animals↗
PubMed1994

Metabolic implications of low-dose triiodothyronine administration in rats: relevance to the adjunctive use of triiodothyronine in the treatment of depression.

The adjunctive use of triiodothyronine (T3) with tricyclic antidepressants is generally believed to augment the efficacy of the tricyclic medications in unipolar, bipolar, and treatment-resistant depression. In the small subset of depressed patients with evidence for overt or subclinical hypothyroidism, the efficacy of supplementary T3 is logically presumed to derive from the amelioration of the hypothyroidism. It is, however, uncertain why adjunctive T3 therapy is often effective in the initially euthyroid depressed patient and if such therapy induces subclinical hyperthyroidism. To determine the metabolic state induced by low-dose T3 treatment, rats were administered nonpulsatile, submaintenance doses of T3 to achieve marked but incomplete suppression of the serum thyroxine (T4) (to 25%-50% of control levels) and serum thyrotropin (TSH) concentrations over a 10-week interval. No statistically significant change in the serum T3 was observed. At sacrifice, multiple parameters of peripheral metabolic status (growth rate, heart rate, organ weights, and tissue alpha-glycerophosphate dehydrogenase activities) in cerebrum, liver, kidney, spleen, and testes were consistent with euthyroidism. Thus, in a centrally regulated T3-predominant environment such as accompanies treatment with submaintenance doses of T3, originally euthyroid animals appear to remain in a euthyroid metabolic state.

Animals↗
PubMed1994

Polyamines mediate coronary transcapillary macromolecular transport in the calcium paradox.

This study addresses the role of polyamines and their rate limiting enzyme, ornithine decarboxylase in regulation of macromolecular transport of two macromolecules, fluorescein and horseradish peroxidase, across coronary capillaries. Rat hearts were isolated and retrogradely perfused through the aorta (Langendorff method), stabilized by 10 min perfusion with Krebs-Henseleit medium containing Ca2+, followed by 5 min perfusion with Krebs-Henseleit medium without Ca2+ and an additional 30 s to 2 min with Krebs-Henseleit medium containing 1 mg/ml horseradish peroxidase. alpha-Difluoromethylornithine, the only known function of which is inhibition of ornithine decarboxylase, and putrescine were added as needed. Perfusion with Krebs-Henseleit medium without Ca2+ caused a two-fold increase in fluorescein transport but a decrease in horseradish peroxidase transport. Reperfusion with Krebs-Henseleit medium caused a four-fold increase in fluorescein transport and a ten-fold increase in horseradish peroxidase positive intraendothelial cell vesicles over control values. alpha-Difluoromethylornithine inhibited these increases and putrescine negated the alpha-difluoromethylornithine effect. Other morphological measures of horseradish peroxidase transport and associated membrane activities including modulation of endothelial cells luminal and abluminal pits were effected in the same manner. Transport of macromolecules through coronary capillaries, over the short term studied, appears to be regulated by the ornithine decarboxylase/polyamine pathway.

Animals↗
PubMed1994

Ethanol modulates calmodulin-dependent Ca(2+)-activated ATPase in synaptic plasma membranes.

The effects of ethanol in vitro on calmodulin-dependent Ca(2+)-activated ATPase (CaM-Ca(2+)-ATPase) activity were studied in synaptic plasma membranes (SPM) prepared from the brain of normal and chronically ethanol-treated rats. In SPM from normal animals, ethanol at 50-200 mM inhibited the Ca(2+)-ATPase activity. Lineweaver-Burk analysis indicates that the inhibition was the result of a decreased affinity of the enzyme for calmodulin, whereas the maximum activity of the enzyme was not changed. Arrhenius analysis indicates that the enzyme activity was influenced by lipid transition of the membranes, and ethanol in vitro resulted in a shift of the transition temperature toward a lower value. From animals receiving chronic ethanol treatment (3 weeks), the SPM were resistant to the inhibitory effect of ethanol on the enzyme activity. The resistance to ethanol inhibition was correlated with a higher enzyme affinity for calmodulin and a higher transition temperature, as compared with normal SPM. Since the calmodulin-dependent Ca(2+)-ATPase in synaptic plasma membranes is believed to be the Ca2+ pump controlling free Ca2+ levels in synaptic terminals, its inhibition by ethanol could therefore lead to altered synaptic activity.

Alcoholism↗
PubMed1994

Regulation of N-methyl-D-aspartate receptor-mediated calcium transport and norepinephrine release in rat hippocampus synaptosomes by polyamines.

The role of polyamines (PA) synthesis in NMDA receptor-mediated 45Ca2+ fluxes and norepinephrine release was studied in rat hippocampal synaptosomes. NMDA (50 microM) caused a sharp (> 2-fold) transient increase in PA synthesis regulating enzyme, ornithine decarboxylase (ODC) activity with concomitant elevation in PA levels in the order putrescine > spermidine > spermine. ODC inhibitor, alpha-difluoromethylornithine (DFMO), and NMDA antagonist, 2-amino-5-phosphonovaleric acid (D-AP5), both blocked increases in ODC activity and PA levels. Activation of NMDA receptors induced a sharp (3 to 4-fold) and quick (15 seconds) increase in 45Ca2+ uptake by synaptosomes within 15 seconds of exposure at 37 degrees C. The efflux of 45Ca2+ and 3H-norepinephrine (NE) release at 22 degrees C from pre-loaded synaptosomes was also significantly (2 to 4-fold) enhanced by NMDA within 15 seconds. These NMDA receptor-mediated effects on calcium fluxes and NE release were blocked by NMDA receptor-antagonists (DAP-5 and MK-801) and PA synthesis inhibitor, DFMO and the DFMO inhibition nullified by exogenous putrescine. These observations establish that ODC/PA cascade play an important role in transduction of excitatory amino acid mediated signals at NMDA receptors.

2-Amino-5-phosphonovalerate↗
PubMed1994

Regulation of calmodulin content in synaptic plasma membranes by glucocorticoids.

Synaptic plasma membranes (SPM) from the brain are known to have specific binding sites for several steroid hormones, but the mechanisms of membrane transduction of steroid signals is not understood. In this study, corticosterone was found to prevent temperature-dependent dissociation of endogenous calmodulin (CaM) from highly purified SPM from rat cerebral cortex. The steroid stabilizes Ca(2+)-dependent membrane binding of endogenous CaM (78% of total CaM), whereas Ca(2+)-independent binding of CaM (the other 22%) is not affected. The stabilization of membrane binding of endogenous CaM by corticosterone is concentration-dependent, with the maximal effect occurring at steroid concentration of 1 microM. The EC50 is estimated as 130 nM, which is almost identical to the Kd of specific binding of the steroid to SPM (120 nM) reported previously. The effect in stabilizing membrane binding of CaM is specific to corticosterone and other glucocorticoids (cortisol, dexamethasone and triamcinolone); gonadal steroids (17 (17 beta-estradiol, progesterone and testosterone) are ineffective. Furthermore, corticosterone administration in vivo (2 mg/kg, i.p.) produced a rapid increase of CaM content in SPM, occurring within 5 min after steroid injection and persisting for at least 20 min. Since CaM mediates a variety of biochemical processes in synaptic membranes, we hypothesize that the effect of glucocorticoids in promoting membrane binding of CaM may lead to a cascade of consequences in synaptic membrane function.

Animals↗
PubMed1994

Correlation between [125I]calmodulin binding and lipid fluidity in synaptic plasma membranes: effects of ethanol and other short-chain alcohols.

Ethanol inhibits [125I]calmodulin binding to synaptic plasma membranes from rat brain, and this inhibition is correlated in a concentration-dependent manner with the increase of membrane fluidity, as determined by diphenylhexatriene fluorescence polarization. Moreover, several short-chain alcohols that increase membrane fluidity are also effective inhibitors of [125I]calmodulin binding. These data support the notion that ethanol inhibits calmodulin binding by increasing lipid fluidity of the synaptic membranes.

Animals↗
PubMed1994

Application of the polymerase chain reaction for the detection of Ehrlichia canis in tissues of dogs.

Doxycycline treatment resulted in a carrier status in 3 dogs and complete clearance of Ehrlichia canis in 2 dogs (Iqbal and Rikihisa, 1994). Using specimens obtained during that study applicability of polymerase chain reactions (PCRs) in detecting E. canis DNA in tissue specimens and correlation of PCR results with our previous cell culture isolation results were evaluated. PCRs using a pair of primers specific to E. canis 16SrRNA gene sequence were used to detect DNA of E. canis in tissues of 5 experimentally-infected dogs 2 months after doxycycline treatment. An approximately 600 bp product defined by the specific primers was amplified in blood, kidney, lymph nodes, liver, and/or spleen of 3 dogs from which E. canis was reisolated in cell culture. In contrast, E. canis DNA was not detected in tissue or blood specimens of the 2 dogs from which E. canis was not reisolated after doxycycline treatment or in 2 control uninfected dogs. The findings indicate PCR is effective in detecting E. canis in tissues.

Animals↗
PubMed1994

Glucocorticoid actions on synaptic plasma membranes: modulation of [125I]calmodulin binding.

The effects of corticosterone on Ca(2+)-dependent binding of [125I]calmodulin to purified synaptic plasma membranes (SPM) from rats brain were characterized. The enhancement of [125I]calmodulin binding was a sigmoidal function of steroid concentration, with the maximal increase (> 55% above control) occurring at a steroid concentration of 1 x 10(-6) M and EC50 estimated at 1-2 x 10(-7) M. Other glucocorticoids including hydrocortisone, dexamethasone and triamcinolone produced similar effects, whereas steroids without glucocorticoid activity such as 11-deoxycortisol, 11-deoxycorticosterone and cholesterol were ineffective. The steroid-induced increase of binding was correlated with an increase of membrane affinity for [125I]calmodulin as shown by Scatchard analysis, and a decrease of the rate of dissociation of [125I]calmodulin from the membranes as shown by kinetic analysis. Arrhenius analysis indicates that [125I]calmodulin binding was influenced by lipid transition of the membranes and that corticosterone resulted in a shift of membrane transition toward a higher temperature. Since a variety of biochemical processes associated with synaptic membranes are dependent upon calmodulin for their regulation, we hypothesize that the effects of glucocorticoids in promoting membrane binding of calmodulin may lead to a cascade of alterations in synaptic function.

Animals↗
PubMed1994

Hydroxylation of progesterone by Cephalosporium aphidicola.

The fungus, Cephalosporium aphidicola, has been shown to hydroxylate progesterone predominantly at the 6 beta- and 11 alpha-positions. Minor metabolites include testosterone acetate, the 20(R)-alcohol and 12 beta, 17 alpha-dihydroxy-progesterone. The sequence involves hydroxylation at 11 alpha and then 6 beta. The hydroxylations of 11 alpha- and 17 alpha-hydroxyprogesterone and of 9 beta, 10 alpha-retroprogesterone have also been examined in the light of these results.

Acremonium↗
PubMed1994

C-reactive protein and alpha 1-acid glycoprotein levels in dogs infected with Ehrlichia canis.

To elucidate whether acute-phase protein responses occur in dogs infected with Ehrlichia canis, C-reactive protein (CRP) and alpha 1-acid glycoprotein (AAG) levels were serially measured in the plasma of five dogs experimentally inoculated with E. canis and 10 sham-inoculated or noninoculated control dogs. The CRP concentration was measured by a canine-specific capture enzyme-linked immunosorbent assay, and the AAG concentration was measured by a canine-specific radial immunodiffusion method. In all E. canis-inoculated dogs, a 3.3- to 6.5-fold increase in the plasma CRP concentration and a 1.9- to 8.6-fold increase in the plasma AAG concentration over the preinoculation level occurred at days 4 to 6 postexposure. Despite the persistence of E. canis and high antibody titers, both CRP and AAG concentrations gradually declined to preexposure levels by day 34 postexposure. E. canis-infected dogs had mild and transient clinical signs which resolved without treatment by day 14 postexposure. The CRP and AAG concentrations in control inoculated or nontreated dogs remained within the normal range throughout the experimental period. Of 12 dogs naturally infected with E. canis, 75% had greater than 50 micrograms of CRP per ml and 83% had greater than 500 micrograms of AAG per ml. All of these 12 dogs had chronic and severe clinical signs of canine ehrlichiosis. Thus, elevations in the levels of acute-phase proteins occur in both acute and chronic canine ehrlichiosis. Determination of CRP and AAG concentrations may help in assessing the severity of inflammatory damage in dogs with E. canis infections.

Acute-Phase Reaction↗
PubMed1994

Reisolation of Ehrlichia canis from blood and tissues of dogs after doxycycline treatment.

We present evidence that supports the carrier status of dogs experimentally infected with Ehrlichia canis after treatment with doxycycline. Canine ehrlichiosis was induced in five dogs by intravenous inoculation with E. canis-infected DH82 cells. All animals developed mild clinical signs of transient fever, body weight loss, thrombocytopenia, and increased gamma globulin levels in plasma. An indirect fluorescent-antibody test (IFA) revealed that all dogs had seroconverted (titer, 5,120) by day 10 postinoculation (p.i.). E. canis was reisolated from blood samples collected at intervals throughout the 2-month period p.i. Doxycycline was administered orally once daily at 10 mg/kg of body weight per day for 1 week starting at 2 months p.i. Following treatment, gamma globulin levels in plasma were decreased. At necropsy on days 54 to 59 after the start of treatment, spleen, liver, kidney, and lymph nodes were collected for E. canis culture and histopathologic examination. Although the dogs did not show significant clinical signs during or after treatment with the antibiotic, E. canis was reisolated from the blood and tissue samples of three of five dogs. A 16-fold reduction in IFA titer was noted in two dogs which were negative for E. canis reisolation at day 49 after the start of treatment, whereas a zero- to fourfold reduction in IFA titer was seen in the remaining three dogs. Western immunoblot reactions to higher-molecular-size E. canis antigens in the sera of two dogs which were negative for E. canis on blood culture decreased, whereas they remained continuously high or only transiently decreased for the duration of the study for antigens in the sera of three dogs from which E. canis was reisolated. Histopathologically, prominent plasmacytosis in the kidney cortex was present in three dogs from which E. canis was reisolated, whereas the kidney cortices of two dogs had moderate to minor plasmacytosis. These findings pose questions regarding the efficacy, dosage and duration of doxycycline treatment in dogs with E. canis infection. In addition, it was shown that IFA and Western immunoblotting may aid in assessing the efficacy of antibiotic therapy when definitive reisolation procedures are not readily available.

Animals↗