A PRELIMINARY STUDY OF P-5227, a new active tricyclic antipsychotic agent.
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Biomedical subjects
J Iqbal
Publications and source records attributed to J Iqbal.
A preliminary study of Thiothixene in chronic schizophrenics.
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Serological diversity of antigens expressed on the surface of erythrocytes infected with Plasmodium falciparum.
We have studied the surface-antigen phenotypes of infected erythrocytes from children with acute falciparum malaria in the Punjab, Pakistan. Infected erythrocytes from 15 children and their homologous acute and convalescent sera, as well as hyperimmune sera from adults living in the same area, were used to analyse the serological diversity of parasite-associated antigens expressed on the surface of erythrocytes infected with Plasmodium falciparum. Analysis included agglutination, cytoadherence/inhibition of cytoadherence to melanoma cells, and rosette formation/disruption of rosettes formed between infected and non-infected erythrocytes. We found that isolate-specific antibodies were acquired by all children during convalescence and that there was a high degree of diversity of surface-antigen phenotypes. A majority of the sera either acquired or increased by 2- to 3-fold the capacity to inhibit cytoadherence and/or agglutinate the patient's own infected erythrocytes during convalescence and a strong correlation was found between these 2 activities. Hyperimmune sera from adults agglutinated and/or inhibited cytoadherence of many, but not all, of the isolates. Rosette formation was observed in 11 of the 15 isolates; 38% of the acute and 75% of the convalescent sera had anti-rosette activity on rosettes formed by the patient's own parasites. Among the isolates there was no correlation between rosette formation and binding of infected erythrocytes to melanoma cells. Our data provide good evidence that the children developed isolate-specific antibodies during convalescence from an acute attack of falciparum malaria and suggest that there was a high degree of heterogeneity of antigens expressed on the surface of infected erythrocytes.
Agglutination Tests↗
Effect of angiotensin-converting-enzyme (ACE) inhibitor trandolapril on human diabetic neuropathy: randomised double-blind controlled trial.
BACKGROUND: Diabetes is a common cause of polyneuropathy. The development and progression of nephropathy, retinopathy, and neuropathy are closely related. Angiotensin-converting enzyme (ACE) inhibitors delay progression of both nephropathy and retinopathy. We investigated the effect of ACE inhibition on diabetic neuropathy. METHODS: We recruited 41 normotensive patients with type I or type II diabetes and mild neuropathy into a randomised double-blind placebo-controlled trial. Changes in the neuropathy symptom and deficit scores, vibration-perception threshold, peripheral-nerve electrophysiology, and cardiovascular autonomic function, were assessed at 6 and 12 months. The primary endpoint was the change in peroneal nerve motor conduction velocity. FINDINGS: We found no significant difference at baseline for age, HbA1c, blood pressure, or severity of neuropathy between two groups. There was no change in HbA1c over the treatment period. Peroneal motor nerve conduction velocity (p=0.03) and M-wave amplitude (p=0.03) increased, and the F-wave latency (p=0.03) decreased and sural nerve action potential amplitude increased (p=0.04) significantly after 12 months of treatment with trandolapril compared with placebo. Vibration-perception threshold, autonomic function, and the neuropathy symptom and deficit score showed no improvement in either group. INTERPRETATION: The ACE inhibitor trandolapril may improve peripheral neuropathy in normotensive patients with diabetes. Larger clinical trials are needed to confirm these data before changes to clinical practice can be advocated.
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Novel phthalazinone and benzoxazinone containing thiazolidinediones as antidiabetic and hypolipidemic agents.
We report here the synthesis of a series of 5-[4-[2-[substituted phthalazinones-2(or 4)yl]ethoxy]phenylmethyl]thiazolidine-2,4-diones and 5-[4-[2-[2,3-benzoxazine-4-one-2-yl]ethoxy]phenylmethyl]thiazolidine-2,4-diones and their plasma glucose and plasma triglyceride lowering activity in db/db mice. In vitro PPARgamma transactivation assay was performed in HEK 293T cells. In vitro and in vivo pharmacological studies showed that the phthalazinone analogue has better activity. PHT46 (compound 5a), the best compound in this series, showed better in vitro PPARgamma transactivation potential than troglitazone and pioglitazone. In insulin resistant db/db mice, PHT46 showed better plasma glucose and triglyceride lowering activity than the standard drugs. Pharmacokinetic study in Wistar rats showed good systemic exposure of PHT46. Subchronic toxicity study in Wistar rats did not show any treatment-related adverse effect.
Animals↗
Leptin and the regulation of food intake and the neuroendocrine axis in sheep.
1. Leptin is secreted by fat and acts on the brain. 2. Central infusion of leptin reduces food intake but does not alter endocrine secretions in normally fed sheep. 3. Leptin treatment can correct for altered hormonal secretion in fasted animals. 4. Alterations in bodyweight (leptin status) affect the expression of a number of genes in the hypothalamus that are involved in the regulation of food intake and neuroendocrine function. 5. Leptin receptors are found in both the hypothalamus and pituitary and direct action of leptin can be demonstrated on the somatotrophs in the pituitary.
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Causative agents of acute diarrhoea in the first 3 years of life: hospital-based study.
During the 2 years of the study, 402 patients and an equal number of age- and sex-matched controls were investigated for the presence of diarrhoeal pathogens. Pathogenic organisms were recovered from 277 (68.9%) patients and 97 (24.1%) controls. In the patient group, possible bacterial pathogens were found in 210 (52.2%) cases. Enteropathogenic Escherichia coli (EPEC) was the most frequently found potential pathogen, being recovered in 132 cases (32.8%) with serotypes 026, 086, 0111 and 0124 being the most frequently identified. Other bacterial pathogens identified were enterotoxigenic E. coli (ETEC) 57 (14.2%), Shigella 13 (3.2%) and Salmonella eight (2%). Rotavirus was identified in 33 (8.2%) cases. Mixed bacterial and viral infections were also seen in 26 (6.5%) cases. In the control group, enteric pathogens were recovered from 97 (24.1%) specimens. The most common bacterial pathogen found in this group was again EPEC (40, 9.9%), with serogroups 018, 044, 0111 and 0126 being the most frequent. Giardia lamblia and Entamoeba histolytica were found in 31 (7.7%) and 10 (2.5%) controls, respectively. Rotavirus was found in 16 (4%) controls. The results of both centres where the study was performed (Karachi and Rawalpindi) were compared.
Bacterial Infections↗
An MRI study of lumbar puncture headaches.
We studied 11 patients undergoing a routine lumbar puncture to determine if there were cerebrospinal fluid leaks at the puncture site and whether the maximum volume of leakage correlates with a lumbar puncture headache. Patients completed a headache questionnaire before and after the lumbar puncture. Limited magnetic resonance imaging of the lumbar spine was obtained 8 to 36 hours after the lumbar puncture and two patients also had later imaging. In a blinded fashion, the largest diameter of cerebrospinal fluid leakage into the paraspinous area was determined from T2 weighted magnetic resonance images and the maximum possible fluid volume was calculated. Six patients had a small cerebrospinal fluid leakage (< 10 mL), two had a medium leakage (10 to 110 mL), and three had a large leakage (> 110 mL). The volume of cerebrospinal fluid leakage did not correlate with occurrence of a lumbar puncture headache. The study demonstrates that cerebrospinal fluid usually leaks into the paraspinous area after a lumbar puncture, but the volume of escaped fluid does not correlate with a lumbar puncture headache.
Cerebrospinal Fluid↗
Modified Giemsa staining for rapid diagnosis of malaria infection.
OBJECTIVES: To develop and evaluate a rapid method for the diagnosis of malaria infection by microscopy of stained blood films. SUBJECTS AND METHODS: Blood specimens were collected from randomly selected confirmed malaria cases (n = 75) and suspected malaria cases (n = 175). The microscopy was done on each set of blood films stained by modified and the standard Giemsa staining methods. RESULTS: All the 75 previously diagnosed malaria cases were confirmed by the microscopy of blood films stained by both methods. Forty-nine (28%) of the 175 cases suspected for malaria infection showed malarial parasites on microscopy of blood films stained by both methods. However, due to homogeneous staining and clearer background of the blood films it was possible to determine the parasite species in 65% of the cases on microscopy of the thick films stained with the modified method compared to only 20% with the standard method. Further, the turnaround time for reporting the microscopy test result was 15-20 and 45-50 min with modified and standard staining methods, respectively. CONCLUSION: Our data showed that performance of the modified staining method in detecting malarial parasites was comparable to that of the standard staining method. Moreover, the modified staining method was rapid, easy to use, and reliable.
Animals↗
Skull repair in children.
Skull defects in children may be congenital or acquired after trauma, infection or tumor. For defects that do not close spontaneously a variety of repair (cranioplasty) materials are available including bone, metals and acrylic. Where possible calvarial autogenous bone is preferred, particularly in younger infants, but in older children especially with large defects other methods may be useful.
Acrylates↗
Diagnosis of imported malaria by Plasmodium lactate dehydrogenase (pLDH) and histidine-rich protein 2 (PfHRP-2)-based immunocapture assays.
This study was conducted to evaluate the performance of two rapid non-microscopic assays: Plasmodium lactate dehydrogenase (pLDH) assay (OptiMAL) and Plasmodium falciparum histidine-rich protein 2 (PfHRP-2) assay (ICT Malaria). The assays were used to detect malaria infection in 515 immigrants living in Kuwait. The performance of both assays was compared to that of microscopy of Giemsa-stained thick blood films and to each other. Of the 515 patients tested, 163 were positive for malaria parasites by microscopy of thick blood film. Of these, 87 were infected with Plasmodium vivax parasites, 63 with P. falciparum, 1 with Plasmodium malariae, and 12 had mixed infections of P. falciparum and P. vivax. The PfHRP-2 assay detected 53 P. falciparum infections and, as expected, failed to detect all but one case of P. vivax. Three cases of mixed infections were also not detected by this assay. The pLDH assay detected 56 P. falciparum cases and 77 P. vivax infections but failed to detect 4 cases of mixed infections. Compared to microscopy, the performance of both the assays to diagnose P. falciparum infection was comparable. The sensitivity for the PfHRP-2 assay was 82% with a specificity of 99.0% and for the pLDH assay the sensitivity was 89% with a specificity of 99.5%. The PfHRP-2 assay detected 4 false positive cases, 2 of which were also detected by the pLDH assay. These patients reported treatment with chloroquine in the last 2-5 weeks. Though the immunocapture diagnostic assays may be helpful in certain situations, microscopy of thick blood film is still the method of choice in diagnosing imported malaria.
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Aetiologic agents of diarrhoeal diseases in hospitalised children in Rawalpindi, Pakistan.
The causes of diarrhoea were diagnosed in 250 children and 250 controls, a sample of 3,500 children who reported to the Rawalpindi General Hospital, Pakistan between May 1983 and April 1984. The pathogens identified in children with diarrhoea were enteropathogenic Escherichia coli (EPEC) (43.2%), enterotoxigenic E. coli (14%), rotavirus (9.6%), Shigella spp (3.6%), Salmonella spp (3.2%) and Giardia lamblia (1.2%). Mixed infections were found in 2.4% of patients. The following pathogens were detected in controls: EPEC (14.0%), rotavirus (7.6%), G. lamblia (6.8%) and Entamoeba histolytica (3.2%). The serotypes of E. coli were determined.
Bacteria↗
A year's trial of thiothixene in chronic schizophrenia.
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