Cyproheptadine Regulates Pyramidal Neuron Excitability in Mouse Medial Prefrontal Cortex / 神经科学通报·英文版

Cyproheptadine (CPH), a first-generation antihistamine, enhances the delayed rectifier outward K current (I) in mouse cortical neurons through a sigma-1 receptor-mediated protein kinase A pathway. In this study, we aimed to determine the effects of CPH on neuronal excitability in current-clamped pyramidal neurons in mouse medial prefrontal cortex slices. CPH (10 µmol/L) significantly reduced the current density required to generate action potentials (APs) and increased the instantaneous frequency evoked by a depolarizing current. CPH also depolarized the resting membrane potential (RMP), decreased the delay time to elicit an AP, and reduced the spike threshold potential. This effect of CPH was mimicked by a sigma-1 receptor agonist and eliminated by an antagonist. Application of tetraethylammonium (TEA) to block I channels hyperpolarized the RMP and reduced the instantaneous frequency of APs. TEA eliminated the effects of CPH on AP frequency and delay time, but had no effect on spike threshold or RMP. The current-voltage relationship showed that CPH increased the membrane depolarization in response to positive current pulses and hyperpolarization in response to negative current pulses, suggesting that other types of membrane ion channels might also be affected by CPH. These results suggest that CPH increases the excitability of medial prefrontal cortex neurons by regulating TEA-sensitive I channels as well as other TEA-insensitive K channels, probably I and inward-rectifier Kir channels. This effect of CPH may explain its apparent clinical efficacy as an antidepressant and antipsychotic.

Appetite stimulants for older persons

Anorexia is one of the most common issues in older patients. Although there is a tendency for loss of appetite in older persons due to decreased physical activity and reduced resting metabolic rate, this physiological anorexia of aging can easily develop into progressive anorexia and weight loss. This pathologic anorexia and resultant weight loss is associated with increased morbidity and mortality, especially in the frail elderly. To prevent older persons from entering a vicious cycle of frailty, that is, anorexia-malnutrition-sarcopenia-functional impairment, routine screening for anorexia and malnutrition should be implemented in geriatric clinical practice. All anorexic elderly patients should be strongly encouraged to maintain their nutrition, and appetite stimulants can be considered if non-pharmacological interventions are not effective. Although there are no US or Korea Food and Drug Administration approved medications for geriatric-specific anorexia and weight loss, several appetite stimulants can be prescribed and are used widely. Megestrol acetate is the most widely studied and commonly used of these drugs. Cyproheptadine, dronabinol, mirtazapine, corticosteroids, anabolic steroids (e.g., testosterone or oxandrolone), and growth hormone are also effective in increasing appetite or weight. However, the use of these orexigenic agents should occur only after their benefit-to-risk ratio has been carefully considered.

Cyclic Vomiting Syndrome: A Functional Disorder / 대한소아소화기영양학회지

Cyclic vomiting syndrome (CVS) is a functional disorder characterized by stereotypical episodes of intense vomiting separated by weeks to months. Although it can occur at any age, the most common age at presentation is 3-7 years. There is no gender predominance. The precise pathophysiology of CVS is not known but a strong association with migraine headaches, in the patient as well as the mother indicates that it may represent a mitochondriopathy. Studies have also suggested the role of an underlying autonomic neuropathy involving the sympathetic nervous system in its pathogenesis. CVS has known triggers in many individuals and avoiding these triggers can help prevent the onset of the episodes. It typically presents in four phases: a prodrome, vomiting phase, recovery phase and an asymptomatic phase until the next episode. Complications such as dehydration and hematemesis from Mallory Wise tear of the esophageal mucosa may occur in more severe cases. Blood and urine tests and abdominal imaging may be indicated depending upon the severity of symptoms. Brain magnetic resonance imaging and upper gastrointestinal endoscopy may also be indicated in certain circumstances. Management of an episode after it has started ('abortive treatment') includes keeping the patient in a dark and quiet room, intravenous hydration, ondansetron, sumatriptan, clonidine, and benzodiazepines. Prophylactic treatment includes cyproheptadine, propranolol and amitriptyline. No mortality has been reported as a direct result of CVS and many children outgrow it over time. A subset may develop other functional disorders like irritable bowel syndrome and migraine headaches.

Pharmacologic Therapy for Cancer Anorexia-Cachexia Syndrome

Cancer-related anorexia-cachexia syndrome (CACS) is a hypercatabolic state, characterized by reduced appetite and weight loss due to ongoing loss of skeletal muscle mass and adipose tissue. CACS occurs mainly in patients with advanced cancer; thus, weight loss in CACS is often associated with poor prognosis and decreased survival. A large number of studies have been conducted on various pharmacologic agents for palliation of cancer-related anorexia. The purpose of this article is to review the pre-existing pharmacologic agents used for CACS and to evaluate the evidence from current studies on each pharmacologic agent. First, appetite stimulants such as corticosteroids, progestins, cyproheptadine, and cannabinoid have been shown to be beneficial by improving appetite and helping with weight changes even if they had no effect on survival rate. Several other agents with anti-inflammatory effects (e.g., eicosapentaenoic acid, thalidomide, and melatonin), prokinetic agents (e.g., metoclopramide), anabolic agents (e.g., androgens and growth hormone), antipsychotics (e.g., mirtazapine and olanzapine), and antiemetics have also been studied in patients in CACS; however further investigations would be required to confirm the beneficial effects.

[ effect of intrathecal administration of cocaine and serotonergic antagonist [cyproheptadine] on nociception in rat]

Cocaine by effect on central nervous system inhibits reuptake of monoamines [serotonin, norepinephrine and dopamine] to presynaptic terminal and increases their concentration. Monoamines such as serotonin cause analgesia at the spinal level. This study investigates the effects of systemic and spinal administration of cocaine on pain sensation and the relation between these effects and serotonin. Male Wistar rats [200-250g] were set in groups: saline [i.p], saline/DMSO [i.p], cocaine 25mg/kg [i.p], saline [i.t], saline/DMSO [i.t], cocaine 100micro g/10 micro l [i.t], cyproheptadine 33 micro g/10 micro l [i.t.] and cyproheptadine 33 micro g/10 micro l/cocaine 100 micro g/10 micro l [i.t]. Tail flick latency was measured before and after administration. Intraplantar formalin was used for induction of chemical pain. The data was analyzed by T-Test and ANOVA. Pain in both phases of formalin test was reduced in both cocaine 25mg/kg [i.p] [P<0.01] and cocaine 100 micro g/10 micro l [i.t.] [P<0.01]. However, in cyproheptadine 33 micro g/10 micro l [i.t], was increased in the first phase [P<0.01]. In cyproheptadine 33 micro g/10 micro l/cocaine 100 micro g/10 micro l [i.t.], the part of pain reduction induced by cocaine was reversed, in both phases [P<0.01]. In tail flick test the results of cyproheptadine 33 micro g/10 micro l [i.t.] showed reduced tail flick latency [P<0.001]. Inhibition of serotonin reuptake at the spinal level plays role in analgesic effects of cocaine probably, because release of serotonin from the spinal serotonergic terminals causes inhibition of pain neurons and reduction of pain. In addition, inhibition of spinal serotonin receptors by cyproheptadine reduced part of analgesic effects of cocaine probably

Extraction and determination of cyproheptadine in human urine by DLLME-HPLC method

Novel dispersive liquid-liquid microextraction [DLLME], coupled with high performance liquid chromatography with photodiode array detection [HPLC-DAD] has been applied for the extraction and determination of cyproheptadine [CPH], an antihistamine, in human urine samples. In this method, 0.6 mL of acetonitrile [disperser solvent] containing 30 micro L of carbon tetrachloride [extraction solvent] was rapidly injected by a syringe into 5 mL urine sample. After centrifugation, the sedimented phase containing enriched analyte was dissolved in acetonitrile and an aliquot of this solution injected into the HPLC system for analysis. Development of DLLME procedure includes optimization of some important parameters such as kind and volume of extraction and disperser solvent, pH and salt addition. The proposed method has good linearity in the range of 0.02-4.5 micro g mL[-1] and low detection limit [13.1 ng mL[-1]]. The repeatability of the method, expressed as relative standard deviation was 4.9% [n = 3]. This method has also been applied to the analysis of real urine samples with satisfactory relative recoveries in the range of 91.6-101.0%

Ensaio clínico randomizado, duplo-cego e controlado por placebo de ciproheptadina para estímulo do apetite na fibrose cística / A randomized, double-blind, placebo-controlled trial of cyproheptadine for appetite stimulation in cystic fibrosis

OBJETIVO: O objetivo deste estudo foi determinar se a administração de ciproheptadina é capaz de induzir ganho de peso em pacientes com fibrose cística. MÉTODOS: Foi realizado um estudo duplo-cego, controlado com placebo em dois centros no Brasil. Vinte e cinco pacientes com fibrose cística entre 5 e 18 anos completaram o estudo. Os pacientes foram randomizados em dois grupos, para receber ciproheptadina 4 mg três vezes por dia durante 12 semanas ou placebo. Todos os dados foram coletados no início e no final do período de estudo e incluíram peso, altura e espirometria. RESULTADOS: O ganho de peso médio foi de 0,67 kg e 1,61 kg nos grupos placebo e ciproheptadina, respectivamente (p = 0,036). O índice de massa corporal (IMC) diminuiu 0,07 kg/m² no grupo placebo e aumentou 0,46 kg/m² no grupo intervenção (p = 0,027). A mudança no IMC para a idade (escore z) foi de -0,19 no grupo placebo e 0,20 no grupo ciproheptadina (p = 0,003). O IMC escore z diminuiu 0,19 no grupo placebo e aumentou 0,2 no grupo ciproheptadina (p = 0,003). Alterações na função pulmonar não foram estatisticamente diferentes. CONCLUSÃO: O uso de ciproheptadina em pacientes com fibrose cística foi bem tolerado, apresentando um ganho de peso significativo e um aumento no IMC após 12 semanas. Foi encontrado um tamanho de efeito clinicamente relevante para o peso/idade (escore z) e IMC para idade (escore z). Tais achados sugerem que a prescrição de ciproheptadina pode ser uma abordagem alternativa para pacientes que precisam de suporte nutricional por um curto período de tempo.

OBJECTIVE: To determine whether the administration of cyproheptadine was able to induce weight gain in patients with cystic fibrosis. METHODS: We performed a double-blind, placebo-controlled trial in two centers in Brazil. Twenty-five patients with cystic fibrosis between 5 and 18 years completed the study. Patients were randomized into two groups, to receive either cyproheptadine 4 mg three times per day for 12 weeks or placebo. All data were collected at the beginning and at the end of the study period and included weight, height and spirometry. RESULTS: Average weight gain was 0.67 kg in the placebo group and 1.61 kg in the cyproheptadine group (p = 0.036). Body mass index (BMI) decreased 0.07 kg/m² in the placebo group and increased 0.46 kg/m² in the intervention group (p = 0,027). The change in BMI for age (z score) was -0.19 in the placebo group and +0.20 in the cyproheptadine group (p = 0.003). BMI z score decreased 0.19 in the placebo group and increased 0.2 in the cyproheptadine group (p = 0.003). Changes in pulmonary function were not statistically different. CONCLUSION: Use of cyproheptadine in cystic fibrosis patients was well tolerated, showing a significant weight gain and a significant increase in BMI after 12 weeks. A clinically relevant effect size for weight/age (z score) and body mass index for age (z score) was found. Such findings suggest that the prescription of cyproheptadine can be an alternative approach for patients who need nutritional support for a short period of time.

Síndrome serotonínico pediátrico: reporte de un caso / Serotonin syndrome pediatric: case report

El síndrome serotonínico es un cuadro neurológico agudo debido a hiperactividad serotoninérgica, por la interacción de drogas que refuerzan o mimetizan la acción del neurotrasmisor. La incidencia del síndrome de serotonina es ascendente por la disponibilidad creciente de fármacos serotoninérgicos como los antidepresivos. Por ello es importante que los médicos reconozcan y manejen adecuadamente el síndrome serotonínico. Este reporte de caso se refiere a una intoxicación accidental por el neuroléptico atípico olanzapina en un niño de 2 años, quien desarrolló manifestaciones clínicas como agitación, sudoración, mioclonías, clonus espontáneo e hipertermia, considerados como criterios diagnóstico del cuadro. La terapia consistió en descontaminación interna con lavado gástrico, carbón activado y sulfato de sodio, ciproheptadina, propranolol y furosemida. Su evolución fue satisfactoria. En nuestro país hay disponibilidad de la mayoría de los fármacos causales y tienen amplio uso, por lo que es probable el subregistro del síndrome. De allí la importancia de este reporte de caso

Serotonin syndrome is an acute neurologic picture due to serotonergic hyperactivity, due to the interaction of drugs that enhance or mimic the action of the serotonin. The incidence of serotonin syndrome is rising because of the growing availability of serotonergic drugs such as antidepressants. It is therefore important that clinicians recognize and manage appropriately this syndrome. This case report refers to an accidental poisoning by the atypical neuroleptic olanzapine in a 2 year old boy who developed clinical manifestations such as agitation, sweating, myoclonus, spontaneous clonus and hyperthermia, considered as diagnostic criteria for the syndrome. Therapy consisted of internal decontamination with gastric lavage, activated charcoal and sodium sulfate, cyproheptadine, propranolol and furosemide. The clinical outcome was satisfactory. In our country the majority of the causal drugs are easily available and widely employed, for which reason it is probable that this syndrome is under registered. Hence the importance of this case report

[Study of antinociceptive effects of Ziziphora tenuior and its interference on opioidergic and serotoninergic systems]

Ziziphora tenuior has been used in Iranian folk medicine as an analgesic and for treatment of digestive diseases. This study was designed to investigate the antinociceptive effects of hydroalcoholic extract of Z. tenuior on visceral pain and its possible involvement in opioidergic and serotoninergic systems in male albino N-MRI mice. Antinociceptive effect of was determined by writhing test as a model of visceral pain. A. tenuior extract was administered intraperitonealy [ip] in doses of 50, 75 and 100 mg/kg and antinociceptive effects were compared with indomethacin [5mg/kg, i.p.] and control groups. The most effective dose of the extract was selected for the possible involvement of opioidergic and serotoninergic systems. 15 minutes before administration of the effective dose, animals were studied by pretreatment of opioid antagonist, naloxane [2mg/kg, i.p.] and serotoninergic antagonist, cyproheptadine [4mg/ kg, i.p.] using writhing test. The results of this study showed that hydroalcoholic extract of Z. tenuior at 50, 75 and 100 mg/kg and indomethacin [5mg/kg] induced a significant reduction in pain response compared to the control group [p<0.05], while, pretreatment with naloxane and cyproheptadine inhibited some of the extract induced antinociceptive effects in comparison to control group [p<0.05]. This study indicated that some of the antiniciceptive properties of Z. tenuior are mediated by opioidergic and serotonergic mechanisms, which confirmed the traditional uses of the plant in the treatment of pain

Futura study: evaluation of efficacy and safety of rupatadine fumarate in the treatment of persistent allergic rhinitis / Estudo futura: avaliação da eficácia e segurança do fumarato de rupatadina no tratamento da rinite alérgica persistente

Allergic rhinitis affects 10-30 percent of the population, negatively impacting one's quality of life and productivity. It has been associated with sinusitis, otitis media, sleep disorders, and asthma. Rupatadine is a second generation antihistamine with increased affinity to histamine receptor H1; it is also a potent PAF (platelet-activating factor) antagonist. It starts acting quite quickly, offers long lasting effect, and reduces the chronic effects of rhinitis. AIM: this study aims to assess the efficacy and safety of rupatadine in the treatment of persistent allergic rhinitis. MATERIALS AND METHOD: this is a multi-centric open prospective study. This study included 241 patients from 13 centers in Brazil and was held between October of 2004 and August of 2005. Signs and symptoms of rhinitis and tolerance to medication were analyzed after one and two weeks of treatment. RESULTS: reduction on general scores from 8.65 to 3.21 on week 2 (p<0.001). All signs and symptoms improved significantly in the first day of treatment (p<0.001), except for nasal congestion and secretion, which improved from the second day of treatment (p<0.001). Adverse events occurred in 19.9 percent of the cases, 27.7 percent on week 1. CONCLUSION: rupatadine effectively controls persistent allergic rhinitis; it is safe and presents low incidence of side effects.

A rinite alérgica acomete 10 a 30 por cento da população, interferindo na qualidade de vida e na capacidade produtiva. Está associada à sinusite, otite, roncopatias e asma. A Rupatadina é um anti-histamínico de segunda geração, com elevada afinidade ao receptor histamínico H1 e potente inibição do fator ativador plaquetário (PAF). Tem rápido início de ação, longa duração e reduz os efeitos crônicos da rinite. OBJETIVO: Avaliar a eficácia e segurança da rupatadina no tratamento da rinite alérgica persistente. MATERIAL E MÉTODO: Estudo multicêntrico, aberto, prospectivo. Foram selecionados 241 pacientes em 13 centros no Brasil durante o período de outubro de 2004 a agosto de 2005. Foram analisados os sinais e sintomas da rinite e a tolerabilidade após 1 e 2 semanas. RESULTADOS: Redução do escore geral de 8,65 para 3,21 na semana 2 (p<0,001). Todos os sinais e sintomas melhoraram significativamente, e no primeiro dia de tratamento (p<0,001), com exceção da obstrução e secreção nasal, a partir do segundo dia (P<0,001). A frequência de eventos adversos foi 19,9 por cento, sendo 27,7 por cento na 1ª semana. CONCLUSÕES: A rupatadina é eficaz no controle da rinite alérgica persistente, é segura e apresenta baixos índices de efeitos colaterais.

Germinating seeds of the mung bean, Vigna radiata (Fabaceae), as a model for the preliminary evaluation of cytotoxic effects of drugs

Cytotoxic properties of plant extracts and drugs being developed for cancer treatment are usually evaluated by a variety of in vivo and in vitro tests carried out in animal or plant based models. In the present study we have evaluated the possibility of using the germinating mung beans (Vigna radiata), for rapid and inexpensive screening of drugs exhibiting cytotoxic properties. Mung beans were allowed to germinate either in tap water or in different drug solutions, and parameters like percent germination, increase in radicle length, change in seedling weight and mitotic index of apical root meristems were determined at two time intervals coinciding with the time at which the radicle length in control group was 1.0 to 1.5 cm (time 0, T0) and 48 h later (T48). Methanol extract of Calotropis procera latex as well as drugs like podophyllotoxin, cyclophosphamide, cyproheptadine and aspirin produced a dose-dependent inhibitory effect on seed germination, seed weight gain, radicle growth and mitotic index in the radicle meristems. The inhibitory effect of some of the drugs tested was associated with reduction in water imbibition. Some of the drugs at higher concentrations allowed seed germination to take place but produced radicle decay and seedling weight loss. Our study shows that germinating V radiata beans could be used as a convenient model for the preliminary screening of drugs exhibiting cytotoxic properties.

Observation on therapeutic effect of He's Santong needling methods on cold erythema multiforme / 中国针灸

<p><b>OBJECTIVE</b>To search for an effective therapy for cold erythema multiforme in ham.</p><p><b>METHODS</b>One hundred and eighty cases with cold erythema multiforme in ham were randomly divided into a Santong group (n=90) and a western medicine group (n=90). The Santong group was treated by He's Santong needling methods and Huantiao (GB 30), Fengshi (GB 31), Zusanli (ST 36), etc. were selected. The western medicine group was treated by oral administration of Cinnarizine, Cyproheptadine and Vitamin E. Two weeks later, their therapeutic effects were observed.</p><p><b>RESULTS</b>The cured rate was 68.9% and the recurrence rate was 11.3% in the Santong group, and 33.3% and 53.3% in the western medicine group, with significant differences in the cured rate and the recurrence rate between the two groups (both P<0.01).</p><p><b>CONCLUSION</b>He's Santong needling methods can increase the cured rate and reduce the recurrence rate of cold erythema multiforme in ham.</p>

Acquired Blaschkoid dermatitis.

Acquired Blaschkoid dermatitis characterised by unilateral relapsing inflammatory disease along the lines of Blaschko. A 40-year-old Indian male presented with unilateral erythematous, itchy grouped papules on the left side of the chest, abdomen, back and left arm of 15 days duration. The eruption stopped abruptly at the midline of the torso, completely sparing the right side of the body. The lesions were arranged in whorls and streaks corresponding to the lines of Blaschko. Skin biopsy showed hyperkeratosis and features suggestive of sub-acute spongiotic dermatitis with lymphocytic infiltrate around the blood vessels in the dermis. Patient was diagnosed as a case of Blaschkoid dermatitis. To the best of our knowledge, this is the first case of this condition being reported from India.

Protective effect of rupatadine against oleic acid-induced acute lung injury in rabbits / 药学学报

Acute lung injury (ALI) makes up a spectrum of disease that is commonly defined as "acute non-cardiogenic edematous lung injury". It may contribute to morbidity and mortality in the critically ill patient in the intensive care unit. ALI was induced by oleic acid in rabbits. During the experiment, blood samples were taken from cervical artery and subjected to blood-gas analysis at different time points after oleic acid injection. Shortly after the rabbits were killed at 3 hour after iv OA injection, bronchoalveolar lavage fluid (BALF) was colleted, and the concentrations of protein, platelet-activating factor (PAF), intercellular adhesion molecule-1 (ICAM-1), interleukin 8 (IL-8) in BALF were then measured by ELISA. The ratio of wet to dry weight (W/D) of left lung was calculated to assess alveolar edema. Lung tissue was fixed in formaldehyde and stained with HE, and examined under a light microscope. The OA-induced elevation of arterial blood oxygen pressure was inhibited, as well as PAF, ICAM-1, IL-8 in BALF in rupatadine group. Furthermore, rupatadine also decreased the concentration of protein in BALF and inhibited the increase of the W/D weight ratio significantly. Light microscopic findings showed that the damage in rupatadine groups was far less severe than that in OA model group. Pretreatment with rupatadine has a beneficial effect on acute lung injury induced by oleic acid in rabbits. The ultimate reduction of inflammatory factors was involved, at least in part, in the mechanism of action of rupatadine effects.

Lethal, oedema, haemorrhagic activity of spotted butterfish (Scatophagus argus, Linn) sting extract and its neutralization by antiserum and pharmacological antagonists.

An attempt has been made in this communication to develop antiserum in rabbit against Scatophagus. argus sting extract. Antiserum did not neutralized the sting extract induced proinflammatory and haemorrhagic activity but successfully neutralized lethality upto 2LD50. Cyproheptadine, indomethacin and BW 755C pretreatment significantly reduced sting extract induced proinflammatory activity. The haemorrhagic activity of sting extract was significantly inhibited by temperature, UV-exposure, EDTA, cyproheptadine, indomethacin and BW 755C pretreatment. The results conclude that the local effects of S.argus venom is likely to be mediated through release of mediators and may be encountered by pharmacological antagonists better than the antiserum.

5-HT2 receptor mediated the potentiation of GABA-activated current in the membrane of the dorsal root ganglion neurons of rat / 药学学报

<p><b>AIM</b>To explore the modulation of 5-HT on GABA-activated current (I(GABA)) in the membrane of rat dorsal root ganglion (DRG) neurons and its mechanism.</p><p><b>METHODS</b>Rat DRG neurons were isolated mechanically and enzymatically, on which whole-cell patch clamp recording and repatch technique for intracellular dialysis were performed.</p><p><b>RESULTS</b>In the majority of neurons examined (92.0%, 69/75) GABA induced a concentration-dependent inward current. In neurons sensitive to GABA preapplication of 5-HT produced potentiation effect (82.6% , 57/69) on I(GABA). Preapplication of 5-HT at concentrations of 1 x 10(-6), 1 x 10(-5), 1 x 10(-4) and 1 x 10(-3) mol x L(-1) potentiated I(GABA) by (35 +/- 8)% (n=8), (47 +/- 11)% (n=10), (65 +/- 17)% (n=9) and (75 +/- 18)% (n=11), respectively. This effect was mimicked by alpha-methyl-5-HT (1 x 10(-6) mol x L(-1)), a specific 5-HT2 receptor agonist, and reversed by cyproheptadine, a selective 5-HT2 receptor antagonist. The potentiation of I(GABA) by 5-HT was irrespective to whether the I(5-HT) presents or not in a subset of neurons. The concentration-response curves for GABA before and after pretreatment with 5-HT manifested the same threshold value and similar EC50 (2.0 x 10(-5) and 1.9 x 10(-5) mol x L(-1), respectively) , while the maximal value of I(GABA) for the latter was 33.6% higher than that for the former. Intracellular dialysis with GDP-beta-S or H-7 abolished the potentiation of I(GABA) by 5-HT, while H-9 did not.</p><p><b>CONCLUSION</b>5-HT can potentiate GABA-activated current via PKC-dependent phosphorylation of GABA(A) receptor following the activation of 5-HT2 receptor.</p>

Effects of autacoid inhibitors and of an antagonist on malaria infection in mice

The effects of p-chlorophenylalanine, an inhibitor of serotonin synthesis, indomethacin, an inhibitor of prostaglandin synthesis, cyproheptadine, a serotonin, bradykinin and histamine antagonist, were assessed separately and in combination with chloroquine (CQ) in Vom strains of Swiss albino mice (18-22 g) of either sex infected intraperitoneally with 1 x 10(7) Plasmodium yoelii nigeriensis-induced malaria. As prophylactic, these agents reduced from 31.9 ± 4.5 to 16.1 ± 8.1 percent the level of parasitemia relative to control but had no appreciable activity as curative agents when administered subcutaneously once daily for 4 days after 72 h of parasites innoculum in vivo. However, CQ alone and the combination of these agents with CQ in curative and prophylactic treatments significantly reduced (from 50.3 ± 5.8 to 4.9 ± 0.75 percent) the level of parasitemia (P < 0.05), which was taken only once 72 h after the parasites innoculum. The prophylactic result was shown to produce better results than the curative treatment. The data indicate that inhibitors and an antagonist can reduce the parasitemia load (the extent of damage and the severity of infection) as well as enhance the effects of CQ when combined with it for malaria therapy. The study reveals that the production of autacoids in established infection renders autacoid inhibitors and an antagonist ineffective for radical cure in malarial mice; however, selective inhibition of local hormones implicated in the pathological manifestations of malaria infection by autacoid inhibitors and an antagonist may be a possible pathway to reduce the severity of infection and the associated tissue damage and to enhance the efficacy of available anti-malarials.

Isolation of a haemorrhagic protein toxin (SA-HT) from the Indian venomous butterfish (Scatophagus argus, Linn) sting extract.

A haemorrhagic protein toxin (SA-HT) was isolated and purified from the spine extract of the Indian venomous butterfish, S. argus Linn, by two step ion exchange chromatography. The toxin was homogeneous in native and SDS-PAGE gel. SDS-molecular weight of the toxin was found to be 18.1 +/- 0.09 kDa. SA-HT produced severe haemorrhage on stomach wall but devoid of cutaneous haemorrhage. UV, EDTA, trypsin, protease, cyproheptadine, indomethacin, acetylsalicylic acid and BW755C treatment significantly antagonized the haemorrhagic activity of SA-HT. The toxin produced dose and time dependent oedema on mice hind paw, which was significantly encountered by cyproheptadine, indomethacin and BW755C. SA-HT increased capillary permeability on guinea pig dorsal flank. On isolated guineapig ileum, rat fundus and uterus, SA-HT produced slow contraction which was completely antagonised by prostaglandin blocker SC19220. On isolated rat duodenum, SA-HT produced slow relaxation. SA-HT significantly increased plasma plasmin, serum MDA level and decreased serum SOD level indicating the possible involvement of cyclooxygenase and lipooxygenase pathway.

Síndrome anticolinérgico central por dosis terapéuticas de ciproheptadina: a propósito de un caso / Central anticholinergic syndrome secondary to therapeutic dosage of ciproheptadine. a case reports

Se presenta el caso de un niño de 10 años de edad, que sufrió el síndrome anticolinérgico central por la ingestión de dosis terapéuticas de ciproheptadina. Se aprovecha el tema para realizar una actualización de este síndrome.