Does L-carnitine prevent cadmium-induced damage in gastrointestinal contractility and histological changes in prepubertal rat / ¿La L-carnitina previene el daño inducido por cadmio en la contractilidad gastrointestinal y los cambios histológicos en ratas prepúberes?

SUMMARY: Cadmium (Cd) is the industrial and environmental toxic heavy metal which is found in air, water and soil. Cd, adversely affects many organs in humans such as kidney, intestine, liver, testis and lungs. L-carnitine (LC) is an important agent that plays essential role in energy metabolism. In our study, we aimed to work out whether LC application has any protective effect on intestinal contractility and morphologic damage of prepubertal rat duodenum on Cd-induced toxicity. Twenty eight prepubertal female Wistar rats were divided into four groups. The first group is control (C), second group; Cd group; Cadmium chloride was given 2 mg/kg 28 days with a one-day break by i.p. The third group; Cd+LC, which cadmium chloride was given 2 mg/kg i.p. and LC was given orally by gastric lavage. The LC dose was given as 75 mg/kg. The fourth group; LC, which only LC was given orally. The intestinal segments were isolated and suspended in tissue bath. Contractile responses were induced by acetylcholine (ACh) and relaxation was achieved with phenylephrine. Also the segments were examined for histological changes by light microscopy. Ach-induced contractions were higher in Cd+LC, LC, and control group compared to the Cd group in duodenal segments. The phenylephrine-induced relaxations were lower in Cd groups as compared with Control, Cd+LC and LC group in duodenal segments. In Cd group intestinal morphology was observed to be severely damaged whereas in Cd+LC group the damage was noticeably lower. Cd administration caused severe cellular damage and decreased gastrointestinal motility. Treatment with the LC has affected the gastrointestinal contractility and reduced the damage in intestinal morphology, which occured after Cd application.

El cadmio (Cd) es el metal pesado tóxico industrial y ambiental que se encuentra en el aire, el agua y el suelo. El Cd afecta negativamente a muchos órganos humanos, como los riñones, los intestinos, el hígado, los testículos y los pulmones. La L-carnitina (LC) es un agente importante que juega un rol esencial en el metabolismo energético. El objetivo de este estudio fue determinar si la aplicación de LC tiene algún efecto protector sobre la contractilidad intestinal y el daño morfológico del duodeno de rata prepuberal sobre la toxicidad inducida por Cd. Veintiocho ratas Wistar hembras prepúberes se dividieron en cuatro grupos. El primer grupo control (C), segundo grupo; grupo cd; Se administró cloruro de cadmio 2 mg/kg durante 28 días con un descanso de un día por vía i.p. El tercer grupo; Cd+LC, al que se administró cloruro de cadmio 2 mg/kg i.p. y LC se administró por vía oral mediante lavado gástrico. La dosis de LC se administró como 75 mg/kg. El cuarto grupo; LC, al cual solo LC se administraba por vía oral. Los segmentos intestinales fueron aislados y suspendieron en baño de tejido. Las respuestas contráctiles fueron inducidas por acetilcolina (ACh) y la relajación se logró con fenilefrina. También se examinaron los segmentos en busca de cambios histológicos mediante microscopía óptica. Las contracciones inducidas por Ach fueron mayores en Cd+LC, LC y el grupo control en comparación con el grupo Cd en los segmentos duodenales. Las relajaciones inducidas por fenilefrina fueron menores en los grupos Cd en comparación con el grupo Control, Cd+LC y LC en los segmentos duodenales. En el grupo Cd se observó que la morfología intestinal estaba severamente dañada mientras que en el grupo Cd+LC el daño fue notablemente menor. La administración de Cd causó daño celular severo y disminución de la motilidad gastrointestinal. El tratamiento con LC afectó la contractilidad gastrointestinal y redujo el daño en la morfología intestinal, que ocurría después de la aplicación de Cd.

Pharmacological effects of different chemotypes of Lippia alba (Mill.) N.E. Brown / Efectos farmacológicos de diferentes quimiotipos de Lippia alba (Mill.) N.E. Brown

The Lippia alba species consists of an aromatic plant used in Brazilian traditional medical practice and in the medical practice of several countries as well. Presenting a wide variability in its essential oil chemical composition, the Lippia alba is classified in chemotypes, or chemical races, according to the major constituents contained in its essential oil. Considering the quali and quantitative distribution of the components in the essential oil affect directly its pharmacological properties, which are presented in the medicinal species, this paper proposes a scientific literature review to correlate both biological and pharmacological properties presented by L. alba according to its chemical constitution.

Lippia alba es una planta aromática utilizada en la medicina tradicional de Brasil y de varios países. Con una gran variabilidad en la composición química de su aceite esencial, se clasifica en quimiotipos, o razas químicas, de acuerdo con los constituyentes mayoritarios presentes en el aceite esencial. Dado que la distribución cualitativa y cuantitativa de los componentes del aceite esencial afecta directamente a las propiedades farmacológicas presentadas por la especie medicinal, este trabajo propone realizar una revisión en la literatura científica para correlacionar las propiedades biológicas y farmacológicas de los quimiotipos presentes en el aceite essencial de la L. alba.

Análise comparativa de perfis de dissolução in vitro e in silico de comprimidos de liberação modificada contendo metformina / Comparative analysis of dissolution profiles in vitro and in silico of modified release tablets containing metformin

A dissolução de um fármaco a partir de uma forma farmacêutica (FF) sólida oral é um pré-requisito para que o mesmo seja absorvido pelo organismo e cumpra seus efeitos terapêuticos. O ensaio de dissolução de medicamentos permite avaliar a quantidade de princípio ativo que é liberado a partir de sua FF, mimetizando in vitro o processo que ocorre no trato gastrointestinal (TGI). O DDDPlus® é o único programa de computador dedicado exclusivamente a simular ensaios de dissolução. O objetivo deste trabalho foi avaliar a capacidade do programa de computador DDDPlus® em fornecer perfis de dissolução in silico de comprimidos matriciais contendo metformina semelhantes aos perfis de dissolução in vitro e avaliar a possibilidade de substituir a comparação de perfis de dissolução in vitro de diferentes formulações de comprimidos matriciais contendo metformina pela comparação de perfis de dissolução in silico fornecidos pelo DDDPlus®.Para tanto, um planejamento estatístico foi realizado para obtenção de perfis de dissolução, variando a velocidade das pás e o uso do sinker. Os perfis de dissolução de 3 formulações teste (T1, T2 e T3) de comprimidos de liberação modificada por matriz polimérica contendo metformina foram comparadas pelos métodos de eficiência de dissolução (ED), tempo médio de dissolução (TMD), fator de diferença (f2) e fator de semelhança (f1). Os resultados indicaram o uso do sinker como fator determinante para a ED e TMD. Assim, o método que utilizava o sinker e a velocidade das pás de 50RPM foi utilizado para avaliar 4 produtos comercializados no Brasil. No DDDPlus® os ensaios de dissolução in vitro das formulações T1, T2 e T3 foram otimizadas para a obtenção das constantes de calibração (CC), as CC foram utilizadas para simular os ensaios de dissolução de T1, T2 e T3 em velocidades de 25 e 50RPM. Os perfis de dissolução simulados foram comparados aos perfis observados, resultando em valores de R2. Valores de R2 acima de 0,90 foram obtidos para todas as simulações realizadas utilizando CC de ensaios in vitro que utilizaram sinker, indicando o potencial do programa em auxiliar o desenvolvimento de novas formulações. Valores de R2 abaixo de 0,70 foram obtidos após a simulação de ensaios utilizando CC de ensaios in vitro que não utilizavam o sinker, indicando que o programa de computador não previu a adesão do comprimido ao fundo da cuba de dissolução durante o ensaio. Os perfis de dissolução simulados das formulações T1, T2 e T3 foram comparadas por f1 e f2 com os perfis de dissolução dos produtos do mercado. Tais comparações concluíram que o software não é indicado como substituto dos ensaios in vitro quando se almeja comparar perfis de dissolução

Dissolution of a drug from an oral solid pharmaceutical form (FF) is a prerequisite for it to be absorbed by the body and to fulfill its therapeutic effects. in vitroDrug dissolution assay allows the amount of active principle released from a FF and mimics the in vivo the process that occurs in the gastrointestinal tract (TGI). DDDPlus® is the only computer program dedicated exclusively to simulating dissolution testing. The objective of this work was to evaluate the ability of DDDPlus® software to provide in silico dissolution profiles of matrix tablets containing metformin similar to in vitro dissolution profiles and to evaluate the possibility of replacing in vitro dissolution profiles comparison of different formulations of matrix tablets containing metformin for a comparison of in silico dissolution profiles provided by DDDPlus®. For this purpose, a statistical design was used, varying agitation speed and the use of sinker to obtain dissolution profiles for 3 test formulations (T1, T2 and T3) of polymer matrix-modified release tablets containing metformin. Dissolution profiles were compared by means of dissolution efficiency (ED), mean dissolution time (TMD), difference factor (f2) and similarity factor (f1). The results indicated the use of sinker as a determinant factor for ED and TMD. Thus, the method that used sinker and agitation speed of 50RPM was used to evaluate 4 products commercialized in Brazil. in vitro dissolution tests of the T1, T2 and T3 formulations were optimized using In DDDPlus® to obtain the calibration constants (CC), which were used to simulate dissolution profiles of T1, T2 and T3 at speeds of 25 and 50RPM. in silico dissolution profiles were compared to in vitro dissolution profiles, resulting in R2 values. R2 values above 0.90 were obtained for all simulations performed using CC from in vitro assays using sinker, indicating the potential of the program to assist the development of new formulations. R2 values below 0.70 were obtained after the simulation of assays using CC from in vitro assays that did not use the sinker, indicating that the computer program did not predict adhesion of the tablet to the bottom of the dissolution cell during the assay. The simulated dissolution profiles of the T1, T2 and T3 formulations were compared by f1 and f2 with the dissolution profiles of the market products. Such comparisons concluded that the software is not indicated as a substitute for in vitro assays when comparing dissolution profiles is desired

Icatibant, an inhibitor of bradykinin receptor 2, for hereditary angioedema attacks: prospective experimental single-cohort study / Icatibanto, um inibidor de receptor 2 de bradicinina, para ataques de angioedema hereditário: estudo experimental prospectivo de coorte sem grupo controle

CONTEXT AND OBJECTIVE: Hereditary angioedema (HAE) with C1 inhibitor deficiency manifests as recurrent episodes of edema involving the skin, upper respiratory tract and gastrointestinal tract. It can be lethal due to asphyxia. The aim here was to evaluate the response to therapy for these attacks using icatibant, an inhibitor of the bradykinin receptor, which was recently introduced into Brazil. DESIGN AND SETTING: Prospective experimental single-cohort study on the efficacy and safety of icatibant for HAE patients. METHODS: Patients with a confirmed HAE diagnosis were enrolled according to symptoms and regardless of the time since onset of the attack. Icatibant was administered in accordance with the protocol that has been approved in Brazil. Symptom severity was assessed continuously and adverse events were monitored. RESULTS: 24 attacks in 20 HAE patients were treated (female/male 19:1; 19-55 years; median 29 years of age). The symptoms were: subcutaneous edema (22/24); abdominal pain (15/24) and upper airway obstruction (10/24). The time taken until onset of relief was: 5-10 minutes (5/24; 20.8%); 10-20 (5/24; 20.8%); 20-30 (8/24; 33.4%); 30-60 (5/24; 20.8%); and 2 hours (1/24; 4.3%). The time taken for complete resolution of symptoms ranged from 4.3 to 33.4 hours. Adverse effects were only reported at injection sites. Mild to moderate erythema and/or feelings of burning were reported by 15/24 patients, itching by 3 and no adverse effects in 6. CONCLUSION: HAE type I patients who received icatibant responded promptly; most achieved improved symptom severity within 30 minutes. Local adverse events occurred in 75% of the patients. .

CONTEXTO E OBJETIVO: O angioedema hereditário (AEH) com deficiência de inibidor de C1 manifesta-se por episódios recorrentes de edema envolvendo pele, trato respiratório superior e gastrointestinal. Pode ser letal por asfixia. O objetivo foi avaliar a resposta à terapia dos ataques com icatibanto, inibidor do receptor de bradicinina, recentemente introduzido no Brasil. TIPO DE ESTUDO E LOCAL: Estudo experimental prospectivo de coorte, sem grupo controle, da eficácia e segurança do icatibanto em paciente com AEH. MÉTODOS: Pacientes com diagnóstico confirmado de AEH foram incluídos de acordo com os sintomas, independentemente do tempo de início do ataque. Icatibanto foi administrado segundo protocolo aprovado no Brasil. A gravidade do sintoma foi estabelecida continuamente e os eventos adversos foram monitorados. RESULTADOS: 24 ataques em 20 pacientes com AEH foram tratados (19 F:1 M; 19-55 anos; mediana 29 anos). Os sintomas foram: edema subcutâneo (22/24), dor abdominal (15/24) e obstrução de vias aéreas superiores (10/24). O tempo para o início do alívio foi: 5-10 minutos, 5/24 (20,8%); 10-20, 5/24 (20,8%); 20-30, 8/24 (33,4%); 30-60, 5/24 (20,8%) e 2 horas, 1/24 (4,3%). O tempo para a resolução completa variou de 4,3-33,4 horas. Somente efeitos adversos nos locais das injeções foram relatados. Eritema leve a moderado e/ou sensação de ardor foram relatados por 15/24 pacientes, prurido em 3, e 6 não tiveram efeitos adversos. CONCLUSÃO: Pacientes com AEH tipo I receberam icatibanto com pronta resposta; a maioria teve melhora na gravidade dos sintomas em 30 minutos. Eventos adversos locais ocorreram em 75% dos pacientes. .

review of the clinical manifestations, pathophysiology and management of opioid bowel dysfunction and narcotic bowel syndrome

Opioids are widely used for the treatment of malignant and non-malignant pains. These medications are accompanied by adverse effects, in particular gastrointestinal symptoms known as opioid bowel dysfunction [OBD]. The most common symptom of OBD is refractory constipation that is usually stable regardless of the use of laxatives. Narcotic bowel syndrome [NBS] is a subset of OBD described as ambiguous chronic pain aggravated by continual or increased opioid use for pain relief. Pathophysiology of these disorders are not definitely disentangled. Some challenging hypothesis have been posed leading to specific management in order to mitigate the adverse effects. This article is a review of the literature on the prevalence, pathophysiology and management of OBD and NBS.

Assessment of Cedrus deodara root oil on the histopathological changes in the gastrointestinal tissues in rats

The present study was designed to investigate the effect of Cedrus deodara root oil on the histopathology of different gastrointestinal organs of Wistar rats. This oil was used traditionally as an anti-ulcer agent in the Indus Unic System and extracted from the plant root by destructive distillation method. A total of 90 rats were taken and divided into groups A, B and C, each comprising of 30 animals. The animals of group B and C were given 0.5 ml/kg and 2.5 ml/kg of C. deodara oil respectively while group A served as control and administered vehicle only. The treatment was given to the animals ones only for 24 hours. All animals were sacrificed and the organs like esophagus, stomach and ileum were taken out. Tissue processing and staining procedure was then carried out for any pathological changes in the animal tissues during microscopic examination. The results indicated that Cedurs deodara root oil at both doses 0.5ml/ kg and 2.5 ml/kg exhibited some adverse effects such as erosion of epithelium, edema on sub-mucosal and mucosal layers, congestion of blood vessels as well as presence of inflammatory cells on esophagus, stomach and ileum were seen. Moreover shortening of villi was also seen at both doses. A study conducted on mammalian toxicity previously on rats revealed that the C. deodara root oil used is not very toxic and comes under least toxic group as standardized by toxicologists. Based on the results obtained it was concluded that C. deodara root oil produced some adverse changes in the tissues of GIT when given at 0.5 ml/kg and 2.5 ml/kg doses but the effects were not lethal therapeutically at this dose LC[50] 16.5 ml/kg. The plant oil showed some toxicity and needs further detailed studies to assess its potential toxicity and therapeutic status before using this material as drug

usage of opioids and their adverse effects in gastrointestinal practice: a review

Opium is one of the oldest herbal medicines currently used as an analgesic, sedative and antidiarrheal treatment. The effects of opium are principally mediated by the micro-, kappa- and delta-opioid receptors. Opioid substances consist of all natural and synthetic alkaloids that are derived from opium. Most of their effects on gastrointestinal motility and secretion result from suppression of neural activity. Inhibition of gastric emptying, increase in sphincter tone, changes in motor patterns, and blockage of peristalsis result from opioid use. Common adverse effects of opioid administration include sedation, dizziness, nausea, vomiting, constipation, dependency and tolerance, and respiratory depression. The most common adverse effect of opioid use is constipation. Although stool softeners are frequently used to decrease opioid-induced bowel dysfunction, however they are not efficacious. Possibly, the use of specific opioid receptor antagonists is a more suitable approach. Opioid antagonists, both central and peripheral, could affect gastrointestinal function and visceromotor sensitivity, which suggests an important role for endogenous opioid peptides in the control of gastrointestinal physiology. Underlying diseases or medications known to influence the central nervous system [CNS] often accelerate the opioid's adverse effects. However, changing the opioid and/or route of administration could also decrease their adverse effects. Appropriate patient selection, patient education and discussion regarding potential adverse effects may assist physicians in maximizing the effectiveness of opioids, while reducing the number and severity of adverse effects

Assessment of effects on health due to consumption of bitter bottle gourd (Lagenaria siceraria) juice.

Background & objectives: The bottle gourd (Lagenaria siceraria) is popularly known as lauki, ghia or dudhi in India. Its consumption is advocated by traditional healers for controlling diabetes mellitus, hypertension, liver diseases, weight loss and other associated benefits. However, in last few years there have been reports of suspected toxicity due to consumption of its juice. This led to the constitution of an Expert Committee by Department of Health Research at Indian Council of Medical Research (ICMR), Ministry of Health & Family Welfare, Government of India in October 2010. The committee looked into the issues related to safety of consumption of bottle gourd juice, and this paper presents the findings. Methods: Information on cases of suspected toxicity due to consumption of bottle gourd juice was collected by internet search, advertising on website of ICMR and by writing to State and district health authorities as well as to medical colleges, hospitals and private nursing homes across the country. Results: Three deaths were reported, one from Delhi and two from Uttar Pradesh after consumption of extremely bitter bottle gourd juice. Three persons who died after consumption of freshly prepared bottle gourd juice or juice mixed with bitter gourd (karela) juice were over 59 years of age and had diabetes since last 20 years. This juice was reported to be extremely bitter by all three. Twenty six persons were admitted to various hospitals of the country on complaint of abdominal pain and vomiting following consumption of freshly prepared bottle gourd juice. Diarrhoea and vomiting of blood (haematemesis) was reported in 18 (69.2%) and 19 (73.1%) patients, respectively. Biochemical investigations revealed elevated levels of liver enzymes. More than 50 per cent patients had hypotension. Endoscopic findings showed profusely bleeding stomach with excessive ulceration seen in distal oesophagus, stomach and duodenum in most of the cases. All these patients recovered fully and no sequeale was recorded for any of the cases. Interpretation & conclusions: Cucurbitaceae family, of which bottle gourd is a member contains the toxic tetracyclic triterpenoid compounds called cucurbitacins which are responsible for the bitter taste. There is no known antidote for this toxicity and clinicians treat such cases symptomatically only. The Committee made the following recommendations: (i) The community needs to be educated that bitter tasting bottle gourd juice should not be consumed and in case there is any discomfort, nausea, vomiting, diarrhoea or any feeling of uneasiness after consumption of juice, the person should immediately be taken to a nearby hospital. (ii) Clinicians are suggested that patients coming with symptoms (discomfort, nausea, vomiting, diarrhoea, gastrointestinal bleeding after consumption of juice) should immediately be attended to and general supportive care should be provided, i.e. IV fluids/crystalloids/blood products/ fresh frozen plasma to maintain the haemodynamics and electrolyte balance; Ryle’s tube to be put in for gastric lavage and to assess gastrointestinal (GI) bleed- aspirate to be preserved; Proton pump inhibitors should be given for management of GI bleed and appropriate treatment for other complications should be given. (iii) The possible research areas identified are chemical composition studies on bitter and normal bottle gourd and other members of cucurbitaceae family; animal toxicity studies and studies on interaction between bottle gourd juice and other drugs.

Pharmacological study of aqueous extract of Scoparia dulcis L. on gastrointestinal tract

The research study was conducted in an attempt to analyze the relative pharmacological effect of the aqueous extracts of Scoparia dulcis L. on the gastrointestinal tract. The Gastrointestinal Motility [GI-Motility] test, Castor oil and MgS0[4] induced diarrhoeal tests were performed utilizing laboratory mice. Scoparia dulcis L. showed laxative effect as revealed by the GI-Motility test, the Castor oil induced and MgSO[4] induced diarrhoeal tests

Gastrointestinal and cardiovascular risk of nonsteroidal anti-inflammatory drugs

Nonsteroidal anti-inflammatory drugs [NSAIDs] confer a gastrointestinal [GI] side effect profile and concerns regarding adverse cardiovascular effects have emerged associated with considerable morbidity and mortality. NSAIDs are highly effective in treating pain and inflammation, but it is well recognized that these agents are associated with substantial gastrointestinal toxicity. Cyclo-oxygenase-2 inhibitors may also reduce the risk for gastrointestinal events, although they may increase cardiovascular adverse events. The selection of an appropriate analgesic or antiinflammatory agent with or without gastroprotective therapy should be individualized

Adjuvantes no tratamento da hiperglicemia do diabetes melito tipo 1: [revisão] / Adjunctive therapies to glycaemic control of type 1 diabetes mellitus: [review]

Desde o Diabetes Control and Complications Trial (DCCT), a terapia insulínica intensiva tem sido direcionada para alcançar valores de glicemia e hemoglobina glicada (HbA1c) tão próximos do normal quanto a segurança permita. Entretanto, a hiperglicemia (especialmente a hiperglicemia pós-prandial) e a hipoglicemia continuam a ser um problema no manejo do diabetes tipo 1. O objetivo de associar outras drogas à terapia insulínica é diminuir a glicemia pós-prandial. A terapia adjunta pode ser dividida em três grupos, conforme seu mecanismo de ação: 1. Aumento da ação da insulina (metformina e tiazolidinedionas); 2. Alteração da liberação de nutrientes no trato gastrintestinal (acarbose e amilina); 3. Outros modos de ação [pirenzepina, fator de crescimento insulina-símile (IGF-1) e peptídeo semelhante ao glucagon 1 (GLP-1). Muitos desses agentes mostraram, em estudos de curto prazo, diminuição de 0,5 por cento a 1 por cento na HbA1c, diminuir a hiperglicemia pós-prandial e as doses diárias de insulina.

Since Diabetes Control and Complications Trial (DCCT), intensive therapy has been directed at achieving glucose and glycosylated hemoglobin (HbA1c) values as close to normal as possible regarding safety issues. However, hyperglycemia (especially postprandial hyperglycemia) and hypoglicemia continue to be problematic in the management of type 1 diabetes. The objective of associating other drugs to insulin therapy is to achieve better metabolic control lowering postprandial blood glucose levels. Adjunctive therapies can be divided in four categories based on their mechanism of action: enhancement of insulin action (e.g. the biguanides and thiazolidinediones), alteration of gastrointestinal nutrient delivery (e.g. acarbose and amylin) and other targets of action (e.g. pirenzepine, insulin-like growth factor I and glucagon-like peptide-1). Many of these agents have been found to be effective in short-term studies with decreases in HbA1c of 0.5-1 percent, lowering postprandial blood glucose levels and decreasing daily insulin doses.

Comparative gastrointestinal toxicity of selective cyclooxygenase (COX-2) inhibitors.

Cyclooxygenase (COX-2) inhibitors were developed with the hope that they will cause fewer gastrointestinal adverse effects. Ability of selective as well as nonselective COX inhibitors to alter ischemia-reperfusion induced damage of gastric mucosa and hapten-induced colitis in rats has been compared. Celecoxib (10, 20 and 40 mg/kg(-l)) was significantly more potent at aggravating ischemia-reperfusion injury as compared to nimesulide. Similarly, celecoxib was found to maximally potentiate TNBS-induced colitis, followed by nimesulide and indomethacin. Celecoxib at its highest dose produced maximum deep histological injury. This paradoxic ulcer and colitis aggravating effect of selective COX-2 inhibitors may be explained by suppression of protective prostaglandins generated as a consequence of COX-2 induction in inflammatory states.

Inhibitory effect of sildenafil on gastrointestinal smooth muscle: role of NO-cGMP transduction pathway.

Nitric oxide (NO) is an important neurotransmitter in the gut and has been demonstrated to be a key physiological mediator of non-adrenergic non-cholinergic (NANC) relaxation of gastrointestinal smooth muscle. In the present study the effect of PDE 5 inhibitor sildenafil on the gastrointestinal function (gastric emptying and intestinal transit) has been demonstrated in mice. Sildenafil (0.5-2 mg/kg, po) did not alter the percent gastric emptying however, in higher doses (5, 10 and 30 mg/kg, po) it inhibited the gastric emptying. On acute administration (0.5-5 mg/kg, po) it did not alter the intestinal transit but in higher doses (10 and 30 mg/kg, p.o.) delayed the intestinal transit. Further, the inhibitory effect of sildenafil was significantly blocked by L-NAME (10 mg/kg, ip), a non-selective NOS inhibitor and methylene blue (1 mg/kg, ip), a guanylate cyclase inhibitor. These findings suggest the participation of NO-cGMP transduction pathway in the inhibitory effect of sildenafil (higher doses) on the gastrointestinal smooth muscles and its potential application in patients with nutcracker oesophagus, hypertensive lower oesophageal sphincter (LOS), achalsia and diabetic gastroparesis or colitis where there is a loss of nNOS.

Adverse effects of systemic isotretinoin therapy: a study of 78 patients

Isotretinoin is an effective treatment for severe forms of acne refractory to other therapies, but it is a teratogen and can cause serious side effects. The side effects, in addition to the constitutional features are related to skin, mucosae, eyes, sexual organs, central nervous system, respiratory system and gastrointestinal tract. Deranged biochemical profile may also be seen in few patients. The current study was aimed to determine the frequency of side effects of systemic isotretinoin therapy in patients treated for acne, thereby assessing its safety. During the calendar year 2004, all the acne patients attending the outpatient department of dermatology, Ziauddin Medical University, KDLB campus, Karachi, fulfilling the inclusion criteria, managed on systemic isotretinoin were enrolled. All were taking isotretinoin at a dose of 0.5mg/kg body weight daily. Baseline investigations were performed in all the patients i.e. liver function tests, lipid profile, complete blood picture and renal function tests. They were followed up for any side effects and clinical improvement. The baseline investigations were repeated monthly to see any biochemical and hematological derangements. 78 patients, 42 females [53.8%] and 36 males [46.2%], with ages ranging from 18 to 24 years, were enrolled. 72 patients [92.2%, p<0.001] developed side effects with a variable frequency of at least one feature in each of these subjects. The side effects, in addition to the constitutional features, observed were related to skin [87.2%], mucosae [10.3%], central nervous system [5.2%], eyes [3.8%], reproductive organs [2.6%], respiratory system [1.3%] and gastrointestinal tract [1.3%]. Deranged biochemical profile was also a feature in few patients [6.3%]. The majority of the patients on systemic isotretinoin have side effects, the most common being cutaneous and mucosal but are trivial. Side effects pertaining to the other systems are less frequent

Effect of aqueous leaf extract of Irvingia gabonensis on gastrointestinal tract in rodents.

Effect of the aqueous leaf extract of I. gabonensis on the gastrointestinal tract was investigated on isolated rabbit jejunum, guinea pig ileum, gastrointestinal motility, castor oil-induced diarrhoea in mice and castor oil-induced fluid accumulation in rats. The results showed that the extract exhibited a concentration-dependent relaxation of spontaneous pendular movement of isolated rabbit jejunum and guinea pig ileum, and attenuated both acetylcholine-induced contraction of rabbit jejunum and histamine-induced contraction of guinea pig ileum. The extract (100, 200 and 400 mg/kg) also caused a significant dose-dependent decrease of gastrointestinal motility in mice (40.12, 39.45 and 37.45%), intestinal fluid accumulation in rats (71.43, 81.63 and 83.27%), and remarkably protected mice against castor oil-induced diarrhoea [58.33, 75 and 91.67% (Di Carlo score)] respectively. Preliminary phytochemical screening of the aqueous leaf extract of I. gabonensis revealed the presence of saponins, tannins, phenols and phlobatanins.

Monitoring adverse reaction to steroid therapy in children.

Patients on corticosteroid therapy, specially for a long period are likely to develop many adverse effects related to the therapy. A physician should be conversant with these to ensure early detection, management and prevention, where possible. Thus, all patients on a long-term corticosteroid therapy should have a baseline and 3 monthly assessments for weight, height, blood pressure and other clinical features of Cushing's syndrome. A 2 hours postprandial blood sugar and serum electrolyte estimation should also be included. Ophthalmic evaluation for glaucoma and cataract should be carried out at 6 monthly intervals and densitometry annually for early detection of osteopenia. In addition, a high index of suspicion should be maintained for timely detection of infections, avascular bone necrosis, myopathy and pseudotumor cerebri.

Asparagus racemosus--an update.

Asparagus racemosus (Shatavari) is recommended in Ayurvedic texts for prevention and treatment of gastric ulcers, dyspepsia and as a galactogogue. A. racemosus has also been used successfully by some Ayurvedic practitioners for nervous disorders, inflammation, liver diseases and certain infectious diseases. However, no scientific proof justifying aforementioned uses of root extract of A. racemosus is available so far. Recently few reports are available demonstrating beneficial effects of alcoholic and water extracts of the root of A. racemosus in some clinical conditions and experimentally induced diseases, e.g. galactogogue effect, antihepatotoxic and immunomodulatory activities. The present article includes the detailed exploration of pharmacological properties of the root extract of A. racemosus reported so far.

Mecanismo inhibidor COX-2 y COX-3 en el daño gastrointestinal inducido por AINE en ratas / Mechanism of inhibition OF COX-2 and COX-3 in gastrointestinal damage induced by NSAID in rats

In randomized groups of Wistar rats, the effect inhibitor of selective NASAID over the COX-1, COX-2 and COX-3 the synchronizes inhibition of COX-1 and COX-2, COX-1 and COX-3, COX-2 and COX-3, and COX-1, COX-2 and COX-3 were studied. The conclusions were that the selective inhibition of COX-1, COX-2 and COX-3 no given gastrointestinal damage; the synchronizes inhibition of COX-1 and COX-2 given preferential gastric damage; in contrast the inhibition of COX-2 and COX-3 given massive necrosis preferential in small intestine.