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Biomedical subjects

B Ahmed

Publications and source records attributed to B Ahmed.

At least 19 recordsLinked to original sources
PubMed2005

Safety of vaginal birth after cesarean delivery.

OBJECTIVE: To compare the outcomes of labor induction in women with a history of 1 cesarean section (CS) who undergo trial of labor. METHODS: A prospective observational study of 702 pregnant women who had 1 previous CS was conducted at Women's Hospital, Hamad Medical Corporation, Doha, Qatar, between April 2003 and April 2004. Those with no history of vaginal delivery were assigned to one group and those with a history of vaginal delivery were assigned to another group, and the latter group was then divided into 2 subgroups according to the results of trial of labor. RESULTS: Of these 702 women with a history of 1 CS, 62.4% also had a history of vaginal delivery. After trial of labor, vaginal delivery occurred more often among women with no history of vaginal delivery (64.8%). Moreover, trial of labor resulted in a vaginal delivery more often in women who were delivered only once and by CS (87.7%) than in women who also had a history of vaginal delivery (79.2%). CONCLUSION: These findings indicate that women who have had a CS should strongly consider natural delivery for subsequent pregnancies.

Adult↗
PubMed2004

Combretastatin A-4 phosphate enhances CPT-11 activity independently of the administration sequence.

We evaluated the effect of different intervals and sequences of the vascular targeting agent combretastatin A-4 disodium phosphate (CA4DP) and CPT-11 administration on tumour growth delay and intratumoral uptake of CPT-11 using a syngeneic rhabdomyosarcoma tumour model. Irrespective of the administration sequence, the combination of CA4DP and CPT-11 significantly increases tumour growth delay in comparison with both drugs alone (P<0.001). Intratumoral CPT-11 concentration generally decreased (up to 5-fold) in the combination groups, while SN-38, the active metabolite of CPT-11, increased up to 9-fold. However, the increased amount of intratumoral SN-38 trapping after CA4DP injection did not correlate with the observed tumour growth delay. In conclusion, CA4DP significantly enhances the antitumour effect of CPT-11, which is not greatly influenced by the administration sequence, and which lacks a correlation with the intratumoral trapping of CPT-11 or SN-38. Mechanisms other than trapping are likely to be involved in the chemosensitising capacity of CA4DP.

Animals↗
PubMed2003

Synthesis and antihepatotoxic activity of some heterocyclic compounds containing the 1,4-dioxane ring system.

Silymarin isolated from Silybum marianum is a mixture of three isomers, silybin (1), silydianin (2) and silychristin (3). Silybin is the most active antihepatotoxic agent, and contains a 1,4-dioxane ring in addition to a flavonoid moiety. Based on the skeleton of silybin, we prepared some flavones and coumarins containing the 1,4-dioxane ring system and evaluated them for antihepatotoxic activity against carbon tetrachloride induced hepatotoxicity in albino rats. The degree of protection was determined by measuring biochemical parameters such as serum glutamic oxaloacetic transaminase (SGOT), serum glutamic pyruvate transaminase (SGPT), alkaline phosphatase (ALKP), total protein (TP) and total albumin (TA). The compounds namely 3',4'(1",4"-dioxino) flavone (4f), and 3',4'(2-hydroxy methyl, 1",4"-dioxino) flavone (4g) were found to exhibit a significant activity comparable to standard drug silymarin (silybon-70). Other compounds also exhibited good activity. The structure activity relationship (SAR) was also studied, and where the flavonoid analogues containing a hydroxy methyl group at position-2" in the dioxane ring exhibited superior antihepatotoxic activity in comparison to coumarin derivatives.

Animals↗
PubMed2002

Triumfettoside, a new alkaloidal steroid glycoside and triumfettosterol, a new sterol from Triumfetta flavescens.

The aerial parts of Triumfetta flavescens H. (N. O. Tiliaceae) afforded a new alkaloidal steroid glycoside, characterized as stigma 5(6)-ene-7,22-dione-25-methylamino-3 beta,23 beta-diol-3-O-beta-D- glucoside and designated as triumfettoside (1); and a new sterol identified as stigma 5(6)-ene-7,22-dione-3 beta,23 beta-diol, designated as triumfettosterol (2). Their structures were elucidated on the basis of chemical and spectral analysis.

Chromatography, Thin Layer↗
PubMed2002

Antihepatotoxic activity of Phyllanthus fraternus.

Different fractions of alcoholic extracts of aerial parts and roots of Phyllanthus fraternus Webster (Euphorbiaceae) were screened for antihepatotoxic activity on carbon tetrachloride induced liver damage in albino rats. The degree of protection was measured using biochemical parameters like serum glutamic oxaloacetic transaminase (SGOT), serum glutamic pyruvate transaminase (SGPT), total protein (TP) and total albumin (TA). The methanol fraction was found to be the most active, which was further supported by a significant recovery of hepatocytes in the histopathological study of the liver showing almost complete normalization of the tissues as neither the fatty accumulation nor the necrosis was observed.

Alanine Transaminase↗
PubMed2001

In vivo antitumor effect of vascular targeting combined with either ionizing radiation or anti-angiogenesis treatment.

PURPOSE: Interference with the tumor blood vessels through anti-angiogenesis or vascular targeting can indirectly suppress tumor growth. Vascular targeting of solid tumors, using tubulin-compromising agents, seems a promising and selective novel treatment. We aimed to evaluate the potential (hypothesis-based) benefit from combinations of vascular targeting using combretastatin A-4 phosphate (combreAp) with either ionizing radiation or anti-angiogenesis. METHODS AND MATERIALS: Rhabdomyosarcoma tumor pieces were inplanted subcutaneously (s.c.) in the lower flank region of syngeneic adult WAG/Rij rats. Tumors were grown until different sizes and stratified for the various treatment groups: small (1-3 cm3), medium (3.1-7 cm3), and large (7.1-14 cm3). CombreAp was injected i.p.; injections of TNP-470 were s.c. in the neck area. Localized single-dose (8 Gy) irradiations of tumors were done under Nembutal anesthesia, always 1 day before a single combreAp (25 mg/kg) injection. The TNP-470 treatment (3 times 30 mg/kg in 1 week) started 1 day after a double (8 days interval between both) combreAp administration. Tumor responses were evaluated by the growth delay assay, and statistical significance of tumor growth change was computed. RESULTS: Large tumors responded better to combreAp treatment given alone than did the smaller ones, confirming our previous data with this tumor model. Combining irradiation with combreAp also resulted in a tumor size-dependent growth delay. With small and medium tumor volumes, a similar response was measured after the combination treatment when compared with irradiation only. Large tumors, however, showed a strong (at least additive) increase of the growth delay with the combined therapy; the difference in tumor growth between the two treatment groups was very significant (p < 0.0001). m When TNP-470 was combined with combreAp, no significant lengthening of the growth delay, irrespective of the tumor size, was present with the applied schedule. CONCLUSION: The current data show a significant advantage in the combination of combreAp with irradiation in rhabdomyosarcomas having a large size (7-14 cm3) at treatment. Such a benefit in tumor response was not observed with the smaller tumors, seemingly because irradiation as such was very effective. No significant gain in growth delay for any tumor size was observed when TNP-470, showing efficacy on its own specifically with tumors measuring <7 cm3, was added to the combreAp treatment. This presumably reflects only little angiogenesis during the first week of rhabdomyosarcoma regrowth after the combreAp treatment.

Angiogenesis Inhibitors↗
PubMed2001

Lupeol, a triterpene, inhibits early responses of tumor promotion induced by benzoyl peroxide in murine skin.

The modulating effect of Lupeol [lup-20(29)-en-3 beta -ol], a triterpene found in many fruits and medicinal plants, on benzoyl peroxide-induced tumor promotion responses or tumor promotion in murine skin is described. Benzoyl peroxide is an effective cutaneous tumor promoter acting through the generation of oxidative stress, the induction of ornithine decarboxylase activity and the enhancement of DNA synthesis. Benzoyl peroxide treatment increases cutaneous microsomal lipid peroxidation and hydrogen peroxide generation. The activity of the cutaneous antioxidant enzymes, namely catalase, glutathione peroxidase, glutathione reductase and glutathione S-transferase, is decreased and levels of cutaneous glutathione are depleted. Benzoyl peroxide treatment also induces ornithine decarboxylase activity and enhances [3H]thymidine uptake in DNA synthesis. Prophylactic treatment of mice with lupeol (0.75 and 1.5 mg per animal) 1 hour before benzoyl peroxide treatment resulted in a diminution of benzoyl peroxide-mediated damage. The susceptibility of cutaneous microsomal membrane to lipid peroxidation and hydrogen peroxide generation was significantly reduced (P< 0.01 and P< 0.01, respectively). In addition, depleted levels of glutathione and inhibited activity of antioxidant enzymes were recovered to a significant level (P< 0.01, P< 0.05 and P< 0.01, respectively). Similarly, the elevated ornithine decarboxylase activity and enhanced thymidine uptake in DNA synthesis were inhibited significantly (P< 0.05) in a dose-dependent manner. The protective effect of lupeol was dose dependent in all parameters. The results suggest that lupeol is an effective skin chemopreventive agent that may suppress benzoyl peroxide-induced cutaneous toxicity.

Animals↗
PubMed2001

Hepatoprotective activity of Luffa echinata fruits.

The different extracts of the fruits of Luffa echinata Roxb. (Cucurbitaceae) were tested for their hepatoprotective activity against CCl(4) induced hepatotoxicity in albino rats. The degree of protection was measured by using biochemical parameters like serum glutamic oxalacetic transaminase (SGOT), serum glutamic pyruvate transaminase (SGPT), alkaline phosphatase (ALKP), total protein (TP) and total albumin (TA). The petroleum ether, acetone and methanolic extracts showed a significant hepatoprotective activity comparable with those of Silymarin.

Alanine Transaminase↗
PubMed2001

Percutaneous transhepatic biliary stenting.

OBJECTIVE: Bilary stenting with endoprosthesis is a palliative procedure to relieve malignant biliary obstruction. Percutaneous transhepatic technique has been employed whenever endoscopic technique was not possible or had failed. SETTING: Angiography/intervention suite, department of radiology, Aga Khan University hospital, Karachi. METHODS: We present retrospective analysis of 17 patients with malignant jaundice who were treated with percutaneous techniques after the endoscopic route had failed. RESULTS: The success rate was 94% with placement of single plastic stent in 14 patients, double stents in 3 patients and self-expandable stent in one patient. The overall complication rate was 41% including sepsis, liver abscess, biloma formation, biliary leakage and stent occlusion. There was one procedure related death due to severe sepsis. CONCLUSION: Percutaneous transhepatic biliary stenting is an alternative procedure to relieve malignant biliary obstruction with high complication rate and should be reserved for selected patients in whom endoscopic route has failed.

Adult↗
PubMed2001

Necrosectomy followed by closed cavity lavage for necrotising pancreatitis--report of three cases.

Necrotizing Pancreatitis is a life threatening condition involving pancreas, peripancreatic and retroperitoneal tissues. It's serious regional and systemic involvement causes multiple organ or system failure. Planned and carefully performed necresectomy followed by closed cavity lavage can significantly reduce the mortality and morbidity of this catastrophic condition. Meticulous preoperative resuscitation, preparation and operative necrosectomy followed by continuos irrigation in the postoperative period were done in three consecutive patients. The operative procedure including postoperative management and follow up is reported and analyzed.

Adult↗
PubMed2000

Low frequency damped oscillations of cat visual cortical neurones.

A synchronizing volley of excitation was delivered to cells from the primary visual cortex of the anaesthetized cat by an electrical pulse stimulation of the optic radiations. In intracellular records, this resulted in an initial, fast depolarization of the membrane potential followed by a longer lasting (266 ms) hyperpolarization, and then to small amplitude damped oscillations of the membrane potential. In different cells the number of peaks ranged from 3 to 6, and the amplitude of the first oscillation averaged 3.5 mV. If the pulse stimulation was repeated during visual drive with an optimal bar stimulus, the membrane potential fluctuations were non-linearly enhanced with spike bursts recorded during the depolarized states of the membrane potential. The amplitude of the first oscillation in these cases averaged 6.9 mV. The mean frequency of damped oscillations was 9.9 Hz. The results suggest that these oscillations are mediated by the waxing and waning of the excitatory drive to the recorded neurone.

Action Potentials↗
PubMed2000

The 5-HT3 agent N-(3-chlorophenyl)guanidine (MD-354) serves as a discriminative stimulus in rats and displays partial agonist character in a shrew emesis assay.

RATIONALE: There is some, albeit conflicting, evidence that 5-HT3 receptors might be involved in the actions of abused stimulants. Most studies have focussed on examinations of 5-HT3 antagonists; this might be due to a lack of high-affinity 5-HT3 agonists that readily penetrate the blood-brain barrier. OBJECTIVES: N-(3-Chlorophenyl) guanidine (MD-354) is a member of a novel class of 5-HT3 ligands developed in our laboratories. We have previously demonstrated that MD-354 can exert agonist effects and now further explore this action. METHODS: Rats (n=9) were trained to discriminate 2 mg/kg MD-354 from saline vehicle in a two-lever drug discrimination task (VI-15 s schedule of reinforcement). The actions of agents with 5-HT3 character were evaluated. The emetic and antiemetic actions of MD-354 were also examined using the shrew as test subject. RESULTS: Various agents with demonstrated 5-HT3 agonist properties substituted for the MD-354 stimulus (MD-354 ED50=0.5 mg/kg): quipazine (ED50=0.2 mg/kg), meta-chlorophenylbiguanide (mCPBG, ED50=1.4 mg/kg), 2-methyl 5-HT (ED50=4.5 mg/kg), 1-(2-naphthyl)biguanide (2-NBG, ED50=1.9 mg/kg), and N-(2-naphthyl)guanidine (2-NG, ED50=0.7 mg/kg). Administration of the training dose of MD-354 in combination with the 5-HT3 antagonists zacopride and tropisetron resulted in stimulus antagonism (AD50=0.02 mg/kg); administered alone, however, zacopride engendered 81% MD-354-appropriate responding (ED50=0.03 mg/kg). MD-354 was shown to produce an emetic effect in the shrew at very high doses (i.e., 40 mg/kg); however, when administered in combination with cisplatin, MD-354 behaved as an antiemetic agent at 10 mg/kg. CONCLUSION: Taken together, the results indicate that MD-354 is a 5-HT3 agonist and that it might be an agent with partial agonist activity.

Animals↗
PubMed2000

Expression of the inducible isoform of nitric oxide synthase in pigment cell lesions of the skin.

Nitric oxide (NO) is a small molecule produced during the conversion of L-arginine to L-citrulline by NO synthase (NOS). Several isoforms of NOS exist, of which the Ca2+-independent, inducible NOS (iNOS or NOS2) is most prominently expressed by macrophages. iNOS activity and increased levels of iNOS have been found in various tumours and tumour cell lines but not in normal tissues; however, the precise role of NO in tumour progression has yet to be elucidated. We studied the expression of iNOS in paraffin sections of 41 benign naevi and 52 primary malignant melanomas (MM) of the skin, as well as in 13 metastatic MM. In addition, nitrotyrosine, indicative of NO production and formation of peroxynitrite, was studied in frozen sections of 13 naevi and 30 MM. Virtually all naevi expressed iNOS, but very few expressed nitrotyrosine, indicating either that iNOS in naevi is functionally inactive, or that naevus cells lack reactive oxygen radicals and thus do not form peroxynitrite. Normal melanocytes in adjacent uninvolved skin were unreactive for both markers. In MM, iNOS was most frequently expressed in the 'pure' and 'invasive' radial growth phase (RGP), whereas expression in the vertical growth phase (VGP) and metastatic phase occurred only in 76% of cases; moreover, in these latest phases of tumour progression, iNOS staining was weak and focal. We conclude that iNOS is expressed de novo in most benign pigment cell lesions. In MM (iNOS-generated) NO appears to play an important part in the early steps of invasion (i.e. the 'invasive' RGP), where it may stimulate neo-angiogenesis and may be a prerequisite for further tumour progression; this view is also supported by the finding of iNOS in the associated blood vessels in the papillary dermis. Finally, our data suggest that (iNOS-generated) NO plays a less significant part in the VGP and in metastatic melanoma.

Biomarkers, Tumor↗
PubMed2000

The clinical and biologic significance of abnormal lipid profiles in patients with myelodysplastic syndromes.

Serum lipid profiles were obtained in 108 patients with myelodysplastic syndrome (MDS) and compared to 28 healthy volunteers. Serum cholesterol and low-density and high-density lipoproteins (LDL and HDL) were found to be significantly lower in MDS patients than in normals (p = 0.0001, 0.0038 and 0.037, respectively). This difference was significant for all MDS categories. Serum cholesterol and HDL were negatively related to biopsy cellularity (p = 0.001 and 0.0001, respectively), and serum triglycerides were negatively related to labeling index (p = 0.0003). No differences were noted in the lipid profiles of MDS patients with normal versus abnormal karyotypes. However, low-risk MDS patients with abnormal karyotypes had significantly lower triglyceride levels compared with the high-risk patients (p = 0.027), as did low-risk patients with normal cytogenetics (p = 0.015). Serum HDL levels were significantly higher for the low-risk group with normal cytogenetics as well (p = 0.003). We conclude that serum cholesterol, LDL, and HDL are significantly reduced in MDS patients, probably indicating excessive intracellular lipid biosynthesis in the expanding clone. These relatively simple measurements could serve as important prognostic markers and reliable indicators of disease activity in individual patients. Prospective studies to determine their utility as independent variables that guide the need for active therapeutic intervention are warranted.

Adult↗
PubMed1999

Caspase-mediated cleavage and functional changes of hematopoietic progenitor kinase 1 (HPK1).

Activation of c-Jun N-terminal kinase (JNK) by Fas ligation is caspase-dependent, suggesting that caspases may regulate activators of the JNK pathway. Here, we report that an upstream activator of JNK, hematopoietic progenitor kinase 1 (HPK1), was cleaved during apoptosis. Cleavage of HPK1 was blocked by peptide inhibitors for caspases. HPK1 was efficiently processed by recombinant caspase 3 in vitro. A conserved caspase recognition site, DDVD (amino acids 382 - 385), was found in the HPK1 protein sequence. By testing HPK1 proteins with in vivo and in vitro cleavage assays, we showed that aspartic acid residue 385 is the target for caspases. HPK1 cleavage separated the amino N-terminal kinase domain from the carboxyl C-terminal regulatory domain, and enhanced HPK1 kinase activity. Unlike the full-length HPK1, the N-terminal cleaved product failed to bind adaptor molecules Grb2 (growth factor receptor-bound protein 2) and Crk (CT10 regulator of kinase). The C-terminal fragment, although having three proline-rich domains, bound to Grb2 and Crk less efficiently than the full-length HPK1 protein. Taken together, the cleavage of HPK1 by caspase profoundly changed its biochemical properties.

Apoptosis↗