Controlled release tablet formulations of isoxsuprine hydrochloride using direct compression technique

Isoxsuprine hydrochloride is a peripheral vasodilator. It is advisable to prepare the drug in sustained release dosage forms to improve patient compliance and to achieve a steady state blood level with minimum side effects. Different hydrophilic and hydrophobia polymers in addition to their combinations were used in different ratios to select the best level of the matrix forming material that provides the most sustaining effect. The effect of different types and concentrations of polymers on the release rate of the drug was investigated. The drug release decreased by increasing the concentration of the polymer in all the studied formulations. Tablet formula containing either 30% [w/w] HPMC 15000 or 30% [w/w] Eudragit RSPM gave the most sustaining effect among the single polymers. The drug release rate from tablets prepared using polymer blends is slower compared to that from those containing single polymers. The slowest drug release was obtained from tablet formulae containing: drug, 10% [w/w] HPMC 15000 and 40% [w/w] Eudragit RSPM and drug, 10% [w/w] Eudragit RSPM and 40% [w/w] Eudragit RLPO. The release of isoxsuprine HCl from matrices prepared using single polymer followed Higuchi 's diffusion model However, zero-order release kinetics was elucidated for the release of isoxsuprine HCl from the investigated polymer blends in phosphate buffer [pH 6.8]

Platelet count/bipolar spleen diameter ratio for the prediciton of esophageal varices: the special egyptian situation

Esophageal variceal hemorrhage is a devastating complication of portal hypertension that occurs in approximately one-third of cirrhotic patients. We assessed the value of the platelet count/ bipolar spleen diameter ratio as a noninvasive parameter for the prediction of esophageal varices [EVs] in Egyptian cirrhotic patients. Laboratory and ultrasonographic and imaging variables were prospectively evaluated in 175 patients with liver cirrhosis. All patients underwent upper gastrointestinal endoscopy. Patients with active gastrointestinal bleeding at the time of admission were excluded. The platelet count/ bipolar spleen diameter ratio in patients with Evs was significantly lower than in patients without EVs. In an analysis of the receiver operating characteristic curves [ROCs], we calculated an optimal cutoff value of 939.7 for this ratio, which gave 100% sensitivity and negative predictive values, 86.3% specificity, a 95.6% positive predictive value, and an area under the ROC curve of 0.94 +/- 0.02, reflecting its overall diagnostic accuracy. These findings were extended to a subset analysis of compensated cirrhotic patients. The platelet count/ bipolar spleen diameter ratio has excellent accuracy in the noninvasive assessment of Evs in patients with compensated or decompensated liver cirrhosis. It is easy to calculate and can lower the financial and sanitary burdens of endoscopy units, especially in developing countries

Primary afferent neuron neuropeptides' mrna regulation in experimental periodontitis in the rat

Periodontal disease is a common chronic inflammatory disease in humans, It is believed that neurogenic inflammation plays an important role in pathogenesis of this disorder. Therefore the neuronal expression of the pro-inflammatory mediators are altered. This study was to determine the neuronal profile of neuropeptides mRNA in the trigeminal ganglia in a model of experimental periodontitis in rats, Periodontitis was induced in male rats by intragingival injection of lipopolysaccharide adjacent to the second right mandibular molar, The animals were killed seven days after lipopolysaccharide injection and the right trigeminal ganglia were processed for in situ hybridisation for neuropeptides [beta-preprotachykinin, alpha-calcitonin gene-related peptide mRNAs and somatostatin]. Expression of these neuropeptides' mRNAs was significantly increased only in small neurons in the mandibular division of the trigeminal ganglion from the periodontitis Group. No significant changes in neuropeptide mRNA levels were seen in the maxillary and ophthalmic divisions of the trigeminal ganglia. The upregulation of neuropeptides mRNAs in periodontal disease suggests a role for neurogenic mechanisms in the development of periodontal disease

Neuronal nitric oxide synthase mRNA and protein distribution along the trigeminal pathway: a possible role in mechanism of headache

Nitric oxide [NO] is produced in the nervous system by the activity of the neuronal nitric oxide synthase [nNOS]. Nitric oxide is involved in nociceptive processing and is an important molecule in the regulation of cranial blood flow and arterial diameters. Thus it is a key molecule in the generation of headache. Headaches are hypothesised to be due to neural activation in the trigeminal pathway resulting in vasodilatation of meningeal blood vessels leading to pain. In this study we investigated the cellular source of NO in structures known to be involved in headache by studying the expression of nNOS mRNA and protein along the trigeminal pathway. Fifteen Wistar adult male rats weighing 300-400g were killed by decapitation under brief anesthesia. The dura mater, trigeminal ganglia and trigeminal nerves were removed and processed for in situ hybridization to study nNOS mRNA expression and for immunohistochemistry to study nNOS protein localization. In situ hybridization showed nNOS mRNA expression in all divisions of the trigeminal ganglia, exclusively in neuronal cell bodies. Immunohistochemistry showed nNOS localization in the trigeminal ganglia both in neuronal cell bodies and neuronal process. Neuronal NOS was also localized in trigeminal nerves and in the dura mater. In the dura mater nNOS immunoreactivity was exclusively localized in meningeal nerve fibers but neither in dural vessels nor in dural cells. These data provide evidence that nNOS mRNA and protein are expressed in neuronal but not vascular structures known to be involved in pathogenesis of headache. Therefore, nNOS could be contributing to the production of dural NO which is known to be a key factor in generation of headache

Distribution of cyclooxygenase-3 [COX-3] in rat nervous system

Cyclooxygenase-3 [Cox-3] is a recently identified cyclooxygenase which is inhibited by paracetamol related drugs rather than traditional non-steroidal anti-inflammatory. In this study the distribution of Cox-3 has been studied in the rat nervous system both in the central and peripheral nervous system. Ten adult male Wistar rats weighing 300-400 g were killed by decapitation under brief anesthesia. Nervous system; brains, spinal cords, spinal ganglia and spinal nerves were removed and processed for immunohistochemisty using an antibody raised against Cox-3. Cox-3 was widely distributed in the rat nervous system. The expression appeared mainly neuronal. In the central nervous system, Cox-3 was localized in neurons in the brain and spinal cord. In the brain Cox-3 was highly expressed in cerebral cortex, hippocampus and cerebellum. In the peripheral nervous system Cox-3 was localized in neurons in the spinal ganglia and in the spinal nerves. Cox-3 was widely distributed in the nervous system. Thus, this isoform could be contributing to the generation of the physiological levels of prostaglandins normally for needed for homeostatic regulation in the nervous system. Localisation of Cox-3 in areas associated with nociception and pain such as brain, spinal cord and spinal ganglia support the hypothesis that Cox-3 may be the central target of paracetamol and other related centrally acting analgesics/antipyretics

Immunohistochemical localization of paracetamol sensitive cyclooxygenase [cox-3] in rat trigemino-vascular system: a possible role in the mechanism of migraine/headache pain

Prostaglandins are synthesized by the activity of cyclooxygenase [Cox] isoforms. The newly discovered isoform [Cox-3] has been shown to be potently inhibited by centrally-acting analgesics, such as acetaminophen [paracetamol] which are widely used in treatment of headache. Vascular headaches such as migraine are hypothesized to be due to neural activation in the trigemino-vascular system. This results in vasodilatation of meningeal blood vessels leading to activation of trigeminal sensory afferents and pain. Headache is thus attributable to a neurovascular interaction. In this study the localisation of Cox-3 has been studied in structures known to be involved in pathogenesis of headache including rat dura mater and trigeminal pathway [trigemino-vascular system]. Fifteen adult male Wistar rats weighing 300-400g were killed by decapitation under brief anaesthesia. The dura mater, the trigeminal ganglia and brain were removed and processed for immunohistochemistry using an antibody raised against Cox-3. Dura mater showed Cox-3 immunoreactivity in meningeal blood vessels, perivascular nerve fibres and mast cells. In the trigeminal ganglia, Cox-3 immunoreactivity was localised in neurons of different sizes and in trigeminal nerve fibres. In the brain stem, Cox-3 was localised in neurons in the trigeminal nuclei. These data provide evidence that Cox-3 is expressed in both neuronal and vascular structures known to be involved in pathogenesis of vascular headache. These data support the hypothesis that Cox-3 may be a central target of paracetamol and related analgesics

Experimental schistosomal hepatitis: protective effect of coenzyme-Q10 against the state of oxidative stress

Schistosoma mansoni [S. mansoni] eggs trapped in the host liver elicit a chain of oxidative processes, where they not only trigger the production of reactive oxygen species, but also lead to alteration of the host antioxidant defense mechanisms. Such events may be, at least in part, responsible for the pathology and progression of fibrosis associated with schistosomal hepatitis. This study was designed to fulfill two aims; assessment of protective effect of the antioxidant Coenzyme-Q10 [Co-Q10] against the state of S. mansoni-induced oxidative stress in the liver, and evaluation of the potential role of Co-Q10 as an adjuvant to praziquantel [PZQ]. S. mansoni infected mice were divided into four main groups; group I: control non-treated group. Group II: received Co-Q10 after infection and was sacrificed 8 and 12 weeks post infection. Croup III: treated by single oral dose of PZQ 8 weeks post infection. Group IV: treated by single oral dose of PZQ 8 weeks post infection then was given Co-Q10 for four weeks. The oxidative stress and overall liver function were improved under Co-Q10 therapy as evidenced by significant reduction in oxidative stress markers, and preservation of antioxidant factors. Liver fibrosis was also reduced with a positive impact on liver function. Moreover, addition of Co-Q10 to PZQ therapy caused; significant reduction of liver egg load, significant improvement of the redox status, and lastly decreased liver fibrosis. From this study we concluded that Co-Q10: 1] ameliorated the oxidative stress status, 2] reduced the degree of liver fibrosis, and 3] enhanced the efficacy of classical therapy in experimental S. mansoni-induced hepatitis

Evaluation of different techniques for correction of nasal septal perforation

Perforations of the septum are a well-recognized complication of septal surgery. Most of the post surgical perforations follow the classic Killian submucous resection. Other iatrogenic causes of perforations include cautery, unrecognized or untreated septal hematoma, which becomes complicated by abscess formation and perforation. Twenty patients with septal perforations of less than 2 cm in the cartilagenous septum were selected for this study. Ten cases were repaired with a tragal cartilage-temporoparietal and deep temporal fascia sandwich technique [group 1]. The other ten cases were repaired using endonasal dissection, suture of the borders of the perforation on at least one side and the interposition of a graft of temporal fascia with bone, either a perpendicular plate of ethmoid [four], if available, or mastoid cortex [six], if not [group 2]. A successful complete closure was achieved in three patients, partial closure in other two patients in group 1. While, a complete closure occurred in four patients and a partial closure in three patients in group 2 after an observation time of up to one year. Both techniques may be considered for the repair of septal perforation. The incomplete closure was most probably due to the migration of the graft immediately after surgery. The remaining perforation was in the posterior part of the septum, which was sufficient to relieve the patient of the symptoms. A complete failure of healing may be due to infection. There was no morbidity of the donor site. No major complications were encountered

Induction of leukaemia in chloramphenicol-treated toads

Chloramphenicol has been associated with the development of aplastic anaemia. As it is still widely used in Egypt, we studied its effect on 100 Egyptian toads [Bufo regularis] given a dose of chloramphenicol of 5 mg/40 g body weight for 12 weeks. We found it induced numerous, severe ultrastructural changes in almost all types of leukocytes. These changes were similar to those induced by the chemical carcinogen 7,12-dimethylbenz[a]anthracene in 100 toads used as the carcinogen control group, and similar to those in leukocytes reported in humans with leukaemia. We recommend regulations be applied on the use of this antibiotic in countries where it is still widely used

Part III - operative repair for inguinal hernia in adults

It was clear from the previous operative observations, that defects in the fascia transversalis was an important finding in all types of inguinal herniae. The role of excess properitoneal fat in the production of direct hernia or in increasing the defect in oblique hernia, was also emphasized. The efficiency of the fascia transversalis and peritoneum as materials for repair of the posterior wall of the inguinal canal was proved from biochemical studies and anatomical studies in parts I and II of this work on the herniae of the anterior abdominal wall. Accordingly 2 techniques were described for the repair of 300 cases of inguinal herniae [oblique + direct + combined] using fascia transversalis alone for the oblique and together with peritoneum for the other two types. Evaluation of these techniques in comparison with other conventional procedures was discussed