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Biomedical subjects

N Iqbal

Publications and source records attributed to N Iqbal.

At least 37 records · Page 2Linked to original sources

Post-thaw plasma membrane integrity of bull spermatozoa separated with a Sephadex ion-exchange column.

Previous experiments have established that filtration of bovine semen through a Sephadex ion-exchange column improves its quality before and after freezing. The present study was conducted to determine the post-thaw membrane integrity of bull spermatozoa separated with a Sephadex ion-exchange column and to determine the kind of protection to spermatozoa is provided by glycerol during freezing and thawing. Semen from Holstein bulls diluted in TEST-yolk extender (with and without glycerol) was filtered through a Sephadex ion-exchange column and frozen in liquid nitrogen (-196 degrees C). After thawing, there were more normal acrosomes in filtered spermatozoa than nonfiltered (P < 0.01). Post-thaw plasma membrane integrity and swelling ability in a hypoosmotic solution revealed that the filtered spermatozoa had a stronger (P < 0.005) plasma membranes than the nonfiltered. Filtered spermatozoa demonstrated higher zona-free hamster oocyte penetration than the nonfiltered (30.5 vs 11.5%; P < 0.0005). Spermatozoa extended in TEST-yolk without glycerol had the lowest (P < 0.001) normal acrosomes, intact plasma membranes and swelling ability. Plasma membrane over the post-acrosomal region of the head and post-midpiece region of the tail was more sensitive to damages caused by freezing and thawing than acrosomal and midpiece regions of spermatozoa. Glycerol in the extender provided significant (P < 0.05) protection to the sensitive regions of filtered and nonfiltered spermatozoa during freezing and thawing. Filtered plus glycerolated spermatozoa had the highest (P < 0.01) normal acrosomes, intact plasma membranes and swelling ability. In conclusion, the pre-freezing filtration of bovine semen harvested the spermatozoa possessing stronger plasma membranes which enabled them to endure freezing and thawing stresses. The addition of glycerol to the extender protected the post-acrosomal region of the head and post-midpiece region of the tail of spermatozoa from freezing and thawing shocks.

Journal Article↗

Prevalence of hepatitis B surface antigen and HCV antibodies in hepatocellular carcinoma cases in Karachi, Pakistan.

Hepatocellular carcinoma (HCC) is a common cancer the world over. In Pakistan it has an incidence of 8/ 100,000 per annum. To assess the prevalence of Hepatitis B virus (HBV) and Hepatitis C virus (HCV) infections in biopsy proven cases of HCC a serological study was conducted at Screening Laboratory of Blood Transfusion Services, Jinnah Postgraduate Medical Centre. Of 54 sera of HCC tested for HBV and HCV infections, 67% showed HBV infection, and 33% HCV infection. Among them 24% were positive for both HBV and HCV infections. No HBV and HCV infection was found in 24% cases of HCC. Our findings suggest viral association for most of the HCC cases reported in the country. We suggest an immediate intervention strategy to prevent the spread of HBV and HCV infections by mandatory screening of blood for HBV and HCV infections, and the use of disposable/sterilized needles, instruments for all invasive procedures. For the prevention of vertical transmission of HBV infections all pregnant women should be screened and vaccinated and HBV vaccination should also be included in EPI (expanded programme for immunization).

Carcinoma, Hepatocellular↗

Hepatic hemangioma: a review.

Hemangioma is a common hepatic lesion. The incidence is reported to be around 2%. The etiology of these lesions is unclear. Hemangioma should be regarded as benign with distinct clinicopathological features. Although most patients are asymptomatic, some may present with abdominal mass, cardiac failure, coagulopathy, or rupture. Hemangioma presents a diagnostic challenge. The surgeon should be aware of this lesion to avoid the pitfalls in differential diagnosis. A misinterpretation of hypervascular metastasis may lead to marked mismanagement. We emphasize the necessity of relatively specific and sensitive investigations in the differential diagnosis of a liver nodule. Surgery alone is usually unnecessary. Therapeutic options include steroids, hepatic artery ligation, therapeutic embolizations, radiation therapy, and chemotherapy. Available data suggest a favorable prognosis.

Hemangioma↗

Synthesis and smooth muscle calcium channel antagonist effects of dialkyl 1,4-dihydro-2,6-dimethyl-4-aryl-3,5-pyridinedicarboxylates containing a nitrooxy or nitrophenyl moiety in the 3-alkyl ester substituent.

A group of racemic 3-[2-nitrooxyethyl (1,3-dinitrooxy-2-propyl or 4-nitrophenylethyl)] 5-isopropyl 1,4-dihydro-2,6-dimethyl-4-[2- trifluoromethylphenyl (2-nitrophenyl or 3-nitrophenyl)]-3,5-pyridinedicarboxylates 13-15 were prepared using the Hantzsch reaction that involved the condensation of 2-nitrooxyethyl 9a, 1,3-dinitrooxy-2-propyl 9b or 4-nitrophenylethyl 9c acetoacetate with isopropyl 3-aminocrotonate 11 and 2-trifluoromethyl 12a, 2-nitro 12b or 3-nitro 12c benzaldehyde. In vitro calcium channel antagonist activities were determined using a guinea pig ileum longitudinal smooth muscle assay. Compounds 13-15 exhibited superior, or equipotent, calcium channel antagonist activity (10(-8) to 10(-10) M range) relative to the reference drug nifedipine (IC50 = 1.43 x 10(-8) M). The R1 C-3 ester substituent was a determinant of calcium channel antagonist activity where the potency order was CH2CH2ONO2 > CH2CH2-C6H4-4-NO2 > or = CH(CH2ONO2)2. In contrast, the C-4 R2-aryl substituent (2-CF3-C6H4-, 2-O2N-C6H4- or 3-O2N-C6H4-) was not a major determinant of activity. Compounds 13a-15a, which possess a 3-(2-nitrooxyethyl) ester substituent exhibit superior calcium channel antagonist smooth muscle relaxant activity (IC50 = 10(-10) M range) relative to nifedipine, could serve as potential probes to investigate the in vivo release of nitric oxide (NO) which induces vascular muscle relaxation.

Animals↗

Morphological and hemodynamic assessments of carotid stenosis using quantitative digital subtraction angiography.

BACKGROUND AND PURPOSE: Digital angiography is the best established tool for assessing atheromatous disease of extracranial blood vessels. Advances in computer technology have now made it possible and practicable to extract quantitative information (length, width, cross-sectional area, and flow velocity) from good-quality clinical angiograms, allowing calculation of volume flow and pressure gradient. The technique of quantitative angiography (QA) is used for assessing coronary artery disease, but to date there has been no clinical application in patients with cerebrovascular disease. SUMMARY OF REPORT: We have developed a computer program for off-line analysis of routine digital subtraction angiographic images. From biplanar images, the program reconstructs the angiogram in three dimensions and performs quantitative analysis of each vessel. From this data, the pressure drop from the aortic arch to the circle of Willis is then calculated. We assessed the clinical applicability of QA in five patients investigated for transient ischemic attack. The carotid artery ipsilateral to the symptomatic hemisphere was occluded in one patient and had minor plaque in another. In the remaining three patients, ipsilateral internal carotid artery stenosis was measured by QA as producing area reductions of 55%, 72%, and 88% (equivalent to diameter reductions of 33%, 48%, and 65%, respectively). In these patients, the quantitative stenosis pressure gradients were calculated as 1.2, 3.0, and 3.5 mm Hg. respectively. Further calculation showed that each stenosis contributed to 18%, 24%, and 60%, respectively, of the total carotid pressure gradient from the aortic arch to the circle of Willis. These carotid arteries carried 47%, 42%, and 26%, respectively, of the total cerebral flow. The results of quantitative analysis were validated by comparing, within each patient, the differences in pressure gradients between right and left carotid systems of between right and left vertebral arteries (overall mean difference in pressure gradient, 0.6 +/- 0.5 mm Hg: P = NS). Finally, comparison was made of pressure gradients across the circle of Willis between the carotid and vertebrobasilar circulations (mean difference in pressure gradient, 4.1 +/- 5.3 mm Hg; P = NS). CONCLUSIONS: Quantitative angiography allows determination of the hemodynamic parameters of a vessel or stenosis. It has significant potential, both as a research tool and in routine clinical practice, for the investigation of cerebrovascular disease.

Angiography, Digital Subtraction↗

A randomized double-blind comparative study of terbinafine for 1, 2 and 4 weeks in tinea capitis.

We report a randomized, double-blind study, comparing the relative efficacy and tolerability of oral terbinafine, given for 1, 2 or 4 weeks, in tinea capitis. Of 161 evaluable patients, 53 were treated with terbinafine for 1 week, 51 for 2 weeks and 57 for 4 weeks. Isolated pathogens included Trichophyton violaceum (71.5%), T. tonsurans (14.9%), T. verrucosum (4.3%), Microsporum audouinii (4.3%), M. canis (2.5%), T. schoenleinii (1.9%) and T. mentagrophytes (0.6%). The final evaluation, at 12 weeks, showed cure rates of 73.6, 80.4 and 85.9%, in the respective groups. The adverse effects noted, were not drug related. In our opinion, terbinafine given for 1, 2 or 4 weeks, is equally effective for most cases of tinea capitis.

Adolescent↗

Syntheses, calcium channel agonist-antagonist modulation activities, and voltage-clamp studies of isopropyl 1,4-dihydro-2,6-dimethyl-3-nitro-4-pyridinylpyridine-5-carboxylate racemates and enantiomers.

A novel group of racemic isopropyl 1,4-dihydro-2,6-dimethyl-3-nitro-4-pyridinylpyridine-5-carboxylate isomers [(+/-)-12-14] were prepared using a modified Hantzsch reaction that involved the condensation of nitroacetone with isopropyl 3-aminocrotonate and 2-, 3-, or 4-pyridinecarboxaldehyde. Determination of their in vitro calcium channel-modulating activities using guinea pig ileum longitudinal smooth muscle (GPILSM) and guinea pig left atrium (GPLA) assays showed that the 2-pyridinyl isomer (+/-)-12 acted as a dual cardioselective calcium channel agonist (GPLA)/smooth muscle selective calcium channel antagonist (GPILSM). In contrast, the 3-pyridinyl [(+/-)-13] and 4-pyridinyl [(+/-)-14] isomers acted as calcium channel agonists on both GPLA and GPILSM. The agonist effect exhibited by (+/-)-12 on GPLA was inhibited by nifedipine and partially reversed by addition of extracellular Ca2+. In anesthetized rabbits, the 4-pyridinyl isomer (+/-)-14 exhibited a hypertensive effect that was qualitatively similar to that exhibited by the nonselective agonist Bay K 8644 and the 3-pyridinyl isomer (+/)-13, whereas the 2-pyridinyl isomer (+/-)-12 induced a hypotensive effect similar to that of the calcium channel antagonist nifedipine. Similar results were obtained in a spontaneously hypertensive rat model. In vitro studies showed that the (+)-2-pyridinyl enantiomer (+)-12A exhibited agonist activity on both GPILSM and GPLA, but that the (-)-2-pyridinyl enantiomer (-)-12B exhibited agonist activity on GPLA and antagonist activity on GPILSM. Whole-cell voltage-clamp studies using isolated guinea pig ventricular myocytes indicated that (-)-12B inhibited the calcium current (ICa), that (+)-12A increased slightly ICa, and that (+/-)-12 inhibited ICa but the latter inhibition was less than that for (-)-12B. (-)-12B effectively inhibited ICa at all membrane potentials examined (-40-50 mV), whereas (+)-12A exhibited a weak agonist effect near the peak of the I-V curve. The 2-pyridinyl isomers (enantiomers) 12 represent a novel type of 1,4-dihydropyridine calcium channel modulator that could provide a potentially new approach to drug discovery targeted toward the treatment of congestive heart failure and probes to study the structure-function relationships of calcium channels.

3-Pyridinecarboxylic acid, 1,4-dihydro-2,6-dimethy↗

The effect of caffeine on the pharmacokinetics of acetaminophen in man.

The influence of caffeine (60 mg) was studied on the pharmacokinetic characteristics of acetaminophen (500 mg single dose) in ten healthy male human volunteers in a complete cross-over design. A high-performance liquid chromatography (HPLC) method was used to analyse serum drug concentrations. Caffeine caused a highly significant (p < 0.01) increase in AUC and AUMC, a significant (p < 0.05) increase in Cmax, and a significant (p < 0.05) decrease in clearance (C1/F) of acetaminophen. We conclude that caffeine taken in doses commonly available commercially or in a cup of coffee can significantly potentiate the therapeutic potential of acetaminophen in man.

Acetaminophen↗

The role of serotonin in schizophrenia.

The hypothesis that the LSD psychosis and by inference schizophrenic psychoses are related to dysfunctions in central serotonergic systems, formulated by Woolley and Shaw in the early 1950s was the first testable theory of modern biological psychiatry. Initially, it did not get the scientific attention it deserved. First, because LSD fell into disrepute and was to all intents and purposes banned from human experimentation. Secondly, the antipsychotics were discovered in the same period, and it became clear that these compounds block dopaminergic transmission and hence for many years thereafter the dopaminergic system occupied center stage in biological schizophrenia research. Presently, interest in the relation between serotonin and schizophrenia has been revived, due to the development of serotonin-blocking agents that appear to exert therapeutic effects in schizophrenia. In this paper the evidence for and against a link between serotonergic defects and schizophrenia psychopathology is critically discussed. The conclusion to be reached is threefold. (1) Interruption of certain serotonergic circuits represents an antipsychotic principle. (2) Tentative evidence suggests the involvement of serotonergic dysfunctions in the pathogenesis of schizophrenic psychoses. (3) It is not yet known whether serotonergic lesions contribute directly to the occurrence of schizophrenic psychopathology or via alterations in the dopaminergic system.

Blood Platelets↗

Comparison of bovine sperm capacitation systems for ability of sperm to penetrate zona-free hamster oocytes and bovine oocytes matured in vitro.

Sperm from the same ejaculate were capacitated in calcium-free Tyrode's, modified Tyrode's with bovine follicular fluid or heparin, and TEST-yolk. Capacitated sperm were coincubated with zona-free hamster oocytes at 37 degrees C for 3 h or with bovine cumulus-enclosed oocytes matured in vitro for 8 h at 37 or 39 degrees C. Bovine oocytes were transferred to fertilization medium and incubated for 72 h at 37 or 39 degrees C. Penetration of zona-free hamster oocytes was highest in calcium-free Tyrode's (53.7%), followed by Tyrode's with follicular fluid (50.6%), TEST-yolk (48.6%), and Tyrode's with heparin (34.2%). Penetration of bovine cumulus-enclosed oocytes matured in vitro at 37 degrees C was highest with heparin (48.1%), followed by TEST-yolk (35.0%), calcium-free Tyrode's (32.5%), and follicular fluid (26.4%). Sperm capacitation with heparin, assayed by penetration of bovine oocytes at 39 degrees C, was better at 39 degrees C (77.1%) than at 37 degrees C (46.1%). However, penetration rates in calcium-free Tyrode's and TEST-yolk were higher at 37 degrees C. The capacitation system with heparin at 39 degrees C and bovine oocytes was best followed by the systems using TEST-yolk and calcium-free Tyrode's at 37 degrees C.

Animals↗

Comparison of various bovine sperm capacitation systems for their ability to alter the net negative surface charge of spermatozoa.

Semen was divided into five aliquots and capacitated for 4 or 6 h in calcium-free Tyrode's (37 degrees C), modified Tyrode's bovine follicular fluid (39 degrees C), modified Tyrode's heparin (39 degrees C), and TEST-yolk buffer (4 degrees C) or incubated in BSA-saline (39 degrees C). Sperm before and after capacitation were electrophoresed at 100 V of constant current for 3 and 6 min. Samples were collected, sperm were counted, and percentages of sperm migrating toward the anode at 0 h and 4 or 6 h were calculated. At 0 h, 61 to 80% of the sperm migrated with a net negative charge. After 4 or 6 h, the percentage of sperm migrating toward the anode significantly decreased in all capacitation media but not in the control. The percentage of sperm migrating toward anode was lowest in calcium-free Tyrode's (22.1%) followed by TEST (28.4%), Tyrode's follicular fluid (29.5%), and Tyrode's heparin (42.5%); these values were less than those for the control (56.0%). The movement of live sperm without the influence of current or freeze-killed sperm under the influence of electrical current (control trials) was negligible. Capacitation reduced the net negative surface charge of sperm, the magnitude of which depended on capacitation system. Net negative charge of sperm was inversely associated with efficiency in penetration of zona-free hamster oocytes.

Animals↗

Effect of various capacitation systems on bovine sperm motion characteristics, acrosome integrity, and induction of hyperactivation.

Sperm from the same ejaculate were capacitated in TEST-yolk, calcium-free Tyrode's, modified Tyrode's containing follicular fluid or heparin, and analyzed at 0, 4, 8, and 12 h for motility characteristics and acrosomal integrity. Percentage of motility, progressive motility, progressive velocity, path velocity, curvilinear velocity, linearity, and amplitude of lateral head displacement differed with media and decreased with time. Calcium-free Tyrode's ranked first in maintaining most motility parameters. However, TEST-yolk sperm ranked first for lateral head displacement but last for linearity at each time. Acrosome-reacted sperm increased over time but were not different between TEST-yolk, calcium-free Tyrode's, and heparin at 4 h. The TEST-yolk sperm at 4 h had about twice the hyperactivation (62.3%) of the other sperm capacitation media. Capacitation of bovine sperm was not associated with a specific change in any measured motility parameter. Differences among the efficacies of capacitation systems were unrelated to parameters of sperm motion, hyperactivation, or acrosomal integrity.

Acrosome↗

Enantioselective syntheses and calcium channel modulating effects of (+)- and (-)-3-isopropyl 5-(4-methylphenethyll) 1,4-dihydro-2,6-dimethyl-4-(2-pyridyl)-3,5-pyridinedicarboxylates.

The (+)- and (-)-enantiomers of 3-isopropyl 5-(4-methylphenethyl) 1,4-dihydro-2,6-dimethyl-4-(2-pyridyl)-3,5-pyridinedicarboxylate were synthesized using an efficient highly enantioselective (ee > or = to 96%) variant of the Hantzsch dihydropyridine synthesis. The key step in this procedure involved the asymmetric Michael addition of a metalated chiral aminocrotonate, derived from D-valine or L-valine, respectively, to the Knoevenagel acceptor (Z)-2-isopropoxycarbonyl-1-(2-pyridyl)-but-1-en-3-one. Both enantiomers exhibited a dual cardioselective partial calcium channel agonist (positive inotropic)/smooth muscle selective calcium channel antagonist effect. The relative in vitro smooth muscle calcium channel antagonist activities of the (-):(+) enantiomers was 26:1. In contrast, the (+)-enantiomer exhibited a greater in vitro positive inotropic effect on guinea pig left atrium where the contractile force was maximally increased by 14.8% at a concentration of 1.63 x 10(-8)M.

Animals↗

Validation of volume blood flow measurements using three-dimensional distance-concentration functions derived from digital x-ray angiograms.

RATIONALE AND OBJECTIVES: The authors present phantom validation of a method for computing pulsatile flow waveforms in arterial vessels from high-frame-rate biplane x-ray angiograms. METHODS: The three-dimensional course of a blood vessel is constructed from biplane digital x-ray angiograms. A parametric image of contrast mass versus time and true three-dimensional path length is generated. Adjacent contrast mass-distance profiles are matched to compute instantaneous velocity, which is multiplied by cross-sectional area to yield volume flow. An electromagnetic flowmeter was used to validate flow estimates in a phantom consisting of 150-mm tubes 3, 4, and 6 mm in diameter, orientated 15 degrees, 30 degrees, and 35 degrees to the imaging plane, with flow rates and waveforms expected in vivo. RESULTS: Mean and peak flows were accurate to within 9% and 10%, respectively, for velocities of less than 1 meter/second at a frame rate of 25 frames per second. CONCLUSIONS: A practical method for computing highly pulsatile flow waveforms in vivo in tortuous vessels is presented.

Algorithms↗

The MCPP challenge test in schizophrenia: hormonal and behavioral responses.

In a neuroendocrine challenge paradigm, the present study investigated responses of schizophrenic patients to m-chlorophenylpiperazine (MCPP), a serotonin (5-hydroxytryptamine, 5HT) agonist. In an oral dose of 0.25 mg/kg, MCPP was administered in a placebo-controlled double-blind design to male schizophrenic patients (n = 7) and normal male controls (n = 8). Behavioral (Positive and Negative Syndrome Scale; PANSS) and hormonal (cortisol, prolactin) variables were measured over the subsequent 210 min. The schizophrenic patients experienced an overall exacerbation of psychopathology on MCPP as compared with placebo (p less than 0.05), with specific worsening of PANSS-positive symptoms (p less than 0.025) and PANSS activation (p less than 0.001). In addition, the schizophrenic patients showed significantly lower cortisol (p less than 0.05) and prolactin (p less than 0.05) responses than the normal subjects. The schizophrenic patients had lower peak MCPP blood levels than the normal subjects, although this difference was not statistically significant. The findings are discussed in terms of 5HT receptor(s) sensitivity and the pharmacokinetics of MCPP in schizophrenia.

Adult↗

Desipramine treatment in panic disorder.

Apart from imipramine (IMI), the efficacy of tricyclic antidepressants in panic disorder (PD) has received surprisingly little investigation. The authors report on a 6 week open trial of desipramine (DMI) preceded by a 10 day placebo lead-in, in 15 patients with PD. By week 6, 80% of the patients were globally rated as much or very much improved on a mean dose of 198 mg. Much of the improvement resulted from a reduction in non-panic attack symptomatology (i.e., psychic, somatic and phobic anxiety). Longer duration of illness, male gender and residual psychic anxiety were associated with poorer response in a subgroup of patients. DMI caused minimal intolerable side effects, suggesting possible compliance advantages in comparison to IMI. Beyond supporting the efficacy of DMI in PD, the results of the study point to a significant medication responsive non-panic illness component and caution against over-relying on panic attacks in assessing both illness severity and treatment response.

Adult↗