Simultaneous determination of paracetamol, dextromethorphan, chlorpheniramine, pseudoephedrine and major impurities of paracetamol and pseudoephedrine by using capillary electrophoresis

Abstract A capillary electrophoresis method was developed for the first time and optimized for the determination of paracetamol, pseudoephedrine, dextromethorphan, chlorpheniramine, 4-aminophenol and ephedrine in tablet formulation. Optimum electrophoretic conditions were achieved by using a background electrolyte of 75 mmol L-1 sodium borate buffer at pH 8.0, a capillary temperature of 30°C, a separation voltage of 30 kV and a pressure injection of the sample at 50 mbar for 10 s. Calibration graphs showed a good linearity with a coefficient of determination (R2) of at least 0.999 for all compounds. Intraday and interday precision (expressed as relative standard deviation (RSD) %) were lower than 1.39% for capillary electrophoresis method. The developed method was demonstrated to be simple and rapid for the determination of paracetamol, pseudoephedrine, dextromethorphan, chlorpheniramine, 4-aminophenol and ephedrine in tablet formulation providing recoveries in the range between 99.62 and 100.57% for all analytes.

Colestasis intrahepática del embarazo: forma de presentación temprana y relación con la infección por el virus de la hepatitis C: reporte de casos / Intrahepatic cholestasis of pregnancy: early presentation and relationship with infection by the hepatitis C virus: case reports / Colestase intra-hepática da gravidez: forma de apresentação precoce e sua relação com a infecção por vírus da hepatite C: relato de casos

Se describe los casos de tres pacientes a quien se les realiza diagnóstico de colestasis intrahepática del embarazo (CIE) de aparición temprana. En dos de ellos el diagnóstico se relacionó con infección por el virus de la hepatitis C (VHC). Reconocer que esta enfermedad puede presentarse de manera temprana en el embarazo y su relación con la infección por el VHC es fundamental para hacer un diagnóstico oportuno de ambas enfermedades y tomar las conductas terapéuticas adecuadas, mejorando así el pronóstico materno y fetal.

It is of great importance to acknowledge that this disease can occur early in pregnancy and that its relationship with HCV infection is a key point for a prompt diagnosis, allowing taking timely appropriate therapeutic decisions, aimed at improving the fetal prognosis.

Descrevemos os casos de três pacientes com diagnóstico de colestase intra-hepática da gravidez de início precoce. Em dois deles o diagnóstico estava relacionado à infecção pelo vírus da hepatite C (VHC). Reconhecer que esta doença pode se manifestar precocemente na gravidez e sua relação com a infecção pelo VHC é fundamental para fazer um diagnóstico oportuno de ambas as doenças e assumir condutas terapêuticas adequadas, melhorando assim o prognóstico materno e fetal.

Evaluation of the bioequivalence of two formulations containing the combination of 400 mg of acetaminophen (paracetamol), 4 mg of phenylephrine and 4 mg of chlorpheniramine in capsules: open-label, three-way crossover study, partially replicated in healthy volunteers of both sexes

This study was carried out in order to compare the relative bioavailability of two different formulations containing 400 mg of acetaminophen + 4 mg of phenylephrine hydrochloride + 4 mg of chlorpheniramine maleate, Test formulation (Cimegripe®) and Reference formulation (Resfenol®) in 84 healthy volunteers of both sexes under fasting conditions. The study was conducted in a single dose, randomized, open-label, crossover 3-way and partially replicated. The tolerability was evaluated by the monitoring of adverse events and vital signs, results of clinical and laboratory tests. Plasma concentrations were quantified by validated bioanalytical methods using the ultra-performance liquid chromatography coupled to tandem mass spectrometry. The Cmax, Tmax, AUC0-t, AUC0-inf, T1/2 and Kel pharmacokinetic parameters were calculated from these obtained concentrations. The 90% confidence intervals were constructed for the ratio reference/test from the geometric average of the Cmax and AUC parameters which were comprised between 80% and 125%. Only the Cmax parameter of the phenylephrine was applied the scaled average bioequivalence due to the intraindividual coefficient of variation > 30% obtained, thus extending the acceptance limits of the interval. It can be concluded that the two formulations were bioequivalent in terms of rate and absorption extent and thus interchangeable

Púrpura por Strongyloides stercoralis en un paciente inmunocompetente / Purpura due to Strongyloides stercoralis in an immunocompetent patient

Resumen La infección por Strongyloides stercoralis es una parasitosis frecuente en las regiones tropicales y subtropicales, incluyendo la Amazonía peruana. En pacientes con inmunocompromiso, las manifestaciones clínicas son variadas y es frecuente la diseminación sistémica de la enfermedad, con compromiso de diversos órganos. Las manifestaciones cutáneas son infrecuentes y se describen en pacientes con algún grado de inmunosupresión. Se presenta el caso de un paciente inmunocompetente que desarrolló una púrpura reactiva por una infección por Strongyloides stercoralis crónica. Ante ello, es posible el compromiso cutáneo en pacientes inmunocompetentes con reagudización sistémica por este parásito.

Infection with Strongyloides stercoralis is a common parasitic infection in tropical and subtropical regions, including the Peruvian Amazon. The clinical manifestations are varied in patients with immunocompromised disease, and the systemic spread of the disease is frequent, compromising different organs and systems. Cutaneous manifestations are infrequent, being described in patients with some degree of immunosuppression. We present the case of an immunocompetent patient who developed a reactive purpura due to chronic Strongyloides stercoralis infection. Thus, skin involvement is possible in immunocompetent patients with systemic exacerbation due to this parasite.

Do pediatric medicines induce topographic changes in dental enamel?

Abstract The purpose of the present study was to evaluate the effect of common pediatric liquid medicines on surface roughness and tooth structure loss and to evaluate the pH values of these medicines at room and cold temperatures in vitro. Eighty-four bovine enamel blocks were divided into seven groups (n = 12): G1-Alivium®, G2-Novalgina®, G3-Betamox®, G4-Clavulin®, G5-Claritin®, G6-Polaramine® and G7-Milli-Q water (negative control). The pH was determined and the samples were immersed in each treatment 3x/day for 5 min. 3D non-contact profilometry was used to determine surface roughness (linear Ra, volumetric Sa) and the Gap formed between treated and control areas in each block. Scanning electron microscopy (SEM) and energy dispersive spectrometry (EDS) were also performed. The majority of liquid medicines had pH ≤ 5.50. G1, G4, and G5 showed alterations in Ra when compared with G7 (p < 0.05). According to Sa and Gap results, only G5 was different from G7 (p < 0.05). Alteration in surface was more evident in G5 SEM images. EDS revealed high concentrations of carbon, oxygen, phosphorus, and calcium in all tested groups. Despite the low pH values of all evaluated medicines, only Alivium®, Clavulin®, and Claritin® increased linear surface roughness, and only Claritin® demonstrated the in vitro capacity to produce significant tooth structure loss.

Effect of histamine H1 and H2 receptor antagonists, microinjected into cerebellar vermis, on emotional memory consolidation in mice

This study investigated the effects of histamine H1 or H2 receptor antagonists on emotional memory consolidation in mice submitted to the elevated plus maze (EPM). The cerebellar vermis of male mice (Swiss albino) was implanted using a cannula guide. Three days after recovery, behavioral tests were performed in the EPM on 2 consecutive days (T1 and T2). Immediately after exposure to the EPM (T1), animals received a microinjection of saline (SAL) or the H1 antagonist chlorpheniramine (CPA; 0.016, 0.052, or 0.16 nmol/0.1 µL) in Experiment 1, and SAL or the H2 antagonist ranitidine (RA; 0.57, 2.85, or 5.7 nmol/0.1 µL) in Experiment 2. Twenty-four hours later, mice were reexposed to the EPM (T2) under the same experimental conditions but they did not receive any injection. Data were analyzed using one-way ANOVA and the Duncan test. In Experiment 1, mice microinjected with SAL and with CPA entered the open arms less often (%OAE) and spent less time in the open arms (%OAT) in T2, and there was no difference among groups. The results of Experiment 2 demonstrated that the values of %OAE and %OAT in T2 were lower compared to T1 for the groups that were microinjected with SAL and 2.85 nmol/0.1 µL RA. However, when animals were microinjected with 5.7 nmol/0.1 µL RA, they did not show a reduction in %OAE and %OAT. These results demonstrate that CPA did not affect behavior at the doses used in this study, while 5.7 nmol/0.1 µL RA induced impairment of memory consolidation in the EPM.

Analysis of chlorpheniramine in human urine samples using dispersive liquid-liquid microextraction combined with high-performance liquid chromatography

A simple and environmentally friendly microextraction technique was used for determination of chlorpheniramine (CPM), an antihistamine drug, in human urine samples using dispersive liquid-liquid microextraction (DLLME) followed by high performance liquid chromatography with diode array detection (HPLC-DAD). In this extraction technique, an appropriate mixture of acetonitrile (disperser solvent) and carbon tetrachloride (extraction solvent) was rapidly injected into the urine sample containing the target analyte. Tiny droplets of extractant were formed and dispersed into the sample solution and then sedimented at the bottom of the conical test tube by centrifugation. Under optimal conditions, the calibration curve was linear in the range of 0.055-5.5 µg mL-1, with a detection limit of 16.5 ng mL-1. This proposed method was successfully applied to the analysis of real urine samples. Low consumption of toxic organic solvents, simplicity of operation, low cost and acceptable figures of merit are the main advantages of the proposed technique.

Utilizou-se uma técnica de microextração simples e ambientalmente amigável para a determinação de clorfeniramina (CPM), anti-histamínico, em amostras de urina humana, utilizando a microextração dispersiva líquido-líquido (DLLME), seguida por cromatografia líquida de alta eficiência com detecção por arranjo de diodos (HPLC-DAD). Nesse método de extração, mistura apropriada de acetonitrila (solvente dispersor) e tetracloreto de carbono (solvente de extração) foi injetada rapidamente na amostra de urina contendo o analito alvo. As pequenas gotículas de agente de extração foram formadas e dispersas na solução da amostra e, em seguida, sedimentadas no fundo do tubo cônico de ensaio por centrifugação. Em condições ótimas, a curva de calibração foi linear no intervalo entre 0,055 e 5,5 µg mL-1, com limite de detecção de 16,5 ng mL-1. O método proposto foi aplicado com sucesso na análise de amostras de urina reais. Baixo consumo de solventes orgânicos tóxicos, simplicidade de operação, baixo custo e figuras de mérito aceitáveis são as principais vantagens do método sugerido.

H1 but not H2 histamine antagonist receptors mediate anxiety-related behaviors and emotional memory deficit in mice subjected to elevated plus-maze testing

This study investigated the role of H1 and H2 receptors in anxiety and the retrieval of emotional memory using a Trial 1/Trial 2 (T1/T2) protocol in an elevated plus-maze (EPM). Tests were performed on 2 consecutive days, designated T1 and T2. Before T1, the mice received intraperitoneal injections of saline (SAL), 20 mg/kg zolantidine (ZOL, an H2 receptor antagonist), or 8.0 or 16 mg/kg chlorpheniramine (CPA, an H1 receptor antagonist). After 40 min, they were subjected to the EPM test. In T2 (24 h later), each group was subdivided into two additional groups, and the animals from each group were re-injected with SAL or one of the drugs. In T1, the Student t-test showed no difference between the SAL and ZOL or 8 mg/kg CPA groups with respect to the percentages of open arm entries (%OAE) and open arm time (%OAT). However, administration of CPA at the highest dose of 16 mg/kg decreased %OAE and %OAT, but not locomotor activity, indicating anxiogenic-like behavior. Emotional memory, as revealed by a reduction in open arm exploration between the two trials, was observed in all experimental groups, indicating that ZOL and 8 mg/kg CPA did not affect emotional memory, whereas CPA at the highest dose affected acquisition and consolidation, but not retrieval of memory. Taken together, these results suggest that H1 receptor, but not H2, is implicated in anxiety-like behavior and in emotional memory acquisition and consolidation deficits in mice subjected to EPM testing.

Penfigoide gestacional "Herpes gestationis": revisión a partir de un caso clínico / Gestational pemphigoid "Herpes gestationis": review from a clinical case

La embarazada es susceptible a cambios en la piel y fanéreos que pueden ser fisiológicos como patológicos. El reconocimiento de estas entidades es fundamental para un correcto manejo. La clasificación y nomenclatura de las dermatosis del embarazo ha sido controversial y confusa, principalmente dado el pobre conocimiento que se tiene sobre el origen de estas entidades. El objetivo de esta revisión es informar sobre el conocimiento actual del penfigoide gestacional a partir de un caso clínico, centrándose en su diagnóstico y tratamiento como patología multidiscilpinaria.

The pregnant woman is susceptible to both physiologic and pathologic changes of the skin and appendages. Recognition of these entities is important for appropriate management. The classification and nomenclature have been controversial and confusing, mainly because of the poor knowledge that we have regarding the origin of this entities. The purpose of this review is to contribute to the current knowledge of pemphigoid gestationis, based on a case-report its diagnosis and treatment as a multidisciplinary pathology.

Chlorpheniramine impairs functional recovery in Carassius auratus after telencephalic ablation

We determined the effect of an H1 receptor antagonist on the functional recovery of Carassius auratus submitted to telencephalic ablation. Five days after surgery the fish underwent a spatial-choice learning paradigm test. The fish, weighing 6-12 g, were divided into four groups: telencephalic ablation (A) or sham lesion (S) and saline (SAL) or chlorpheniramine (CPA, ip, 16 mg/kg). For eight consecutive days each animal was trained individually in sessions separated by 24 h (alternate days). Training trials (T1-T8) consisted of finding the food in one of the feeders, which were randomly blocked for each subject. Animals received an intraperitoneal injection of SAL or CPA 10 min after the training trials. The time spent by the animals in each group to find the food (latency) was analyzed separately at T1 and T8 by the Kruskal-Wallis test, followed by the Student Newman-Keuls test. At T1 the latencies (mean ± SEM) of the A-SAL (586.3 ± 13.6) and A-CPA (600 ± 0) groups were significantly longer than those of the S-SAL (226.14 ± 61.15) and S-CPA (356.33 ± 68.8) groups. At T8, the latencies of the A-CPA group (510.11 ± 62.2) remained higher than those of the other groups, all of which showed significantly shorter latencies (A-SAL = 301.91 ± 78.32; S-CPA = 191.58 ± 73.03; S-SAL = 90.28 ± 41) compared with T1. These results support evidence that training can lead to functional recovery of spatial-choice learning in telencephalonless fish and also that the antagonist of the H1 receptor impairs it.

Chlorpheniramine facilitates inhibitory avoidance in teleosts submitted to telencephalic ablation

The present study investigated the involvement of H(1) histaminegic receptor on the acquisition of inhibitory avoidance in Carassius auratus submitted to telencephalic ablation. The fish were submitted to telencephalic ablation 5 days before the experiment. The inhibitory avoidance procedure included 1 day for habituation, 3 days for training composed of 3 trials each (1st day: T1, T2, T3; 2nd day: 2T1, 2T2, 2T3; 3rd day: 3T1, 3T2, 3T3) and 1 day for test. On training days, the fish were placed in a white compartment, after 30 s the door was opened. When the fish crossed to a black compartment, a weight was dropped (aversive stimuli). Immediately after the third trial, on training days, the fish received, intraperitoneally, one of the pharmacological treatments (saline (N = 20), 8 (N = 12) or 16 (N = 13) µg/g chlorpheniramine, CPA). On the test day, the time to cross to the black compartment was determined. The latency of the saline group increased significantly only on the 3rd trial of the 2nd training day (mean ± SEM, T1 (50.40 ± 11.69), 2T3 (226.05 ± 25.01); ANOVA: P = 0.0249, Dunn test: P < 0.05). The group that received 8 µg/g CPA showed increased latencies from the 2nd training day until the test day (T1 (53.08 ± 17.17), 2T2 (197.75 ± 35.02), test (220.08 ± 30.98); ANOVA: P = 0.0022, Dunn test: P < 0.05)). These results indicate that CPA had a facilitating effect on memory. We suggest that the fish submitted to telencephalic ablation were able to learn due to the local circuits of the mesencephalon and/or diencephalon and that CPA interferes in these circuits, probably due an anxiolytic-like effect.

Chloroquine resistant Plasmodium falciparum malaria in Osogbo Nigeria: efficacy of amodiaquine + sulfadoxine-pyrimethamine and chloroquine + chlorpheniramine for treatment

Chloroquine (CQ) resistance in Plasmodium falciparum contributes to increasing malaria-attributable morbidity and mortality in Sub-Saharan Africa. Despite a change in drug policy, continued prescription of CQ did not abate. Therefore the therapeutic efficacy of CQ in uncomplicated falciparum malaria patients was assessed in a standard 28-day protocol in 116 children aged between six and 120 months in Osogbo, Southwest Nigeria. Parasitological and clinical assessments of response to treatment showed that 72 (62.1 percent) of the patients were cured and 44 (37.9 percent) failed the CQ treatment. High initial parasite density and young age were independent predictors for early treatment failure. Out of the 44 patients that failed CQ, 24 received amodiaquine + sulphadoxine/pyrimethamine (AQ+SP) and 20 received chlorpheniramine + chloroquine (CH+CQ) combinations. Mean fever clearance time in those treated with AQ+SP was not significantly different from those treated with CH+CQ (p = 0.05). There was no significant difference in the mean parasite density of the two groups. The cure rate for AQ+SP group was 92 percent while those of CH+CQ was 85 percent. There was a significant difference in parasite clearance time (p = 0.01) between the two groups. The 38 percent treatment failure for CQ reported in this study is higher than the 10 percent recommended by World Health Organization in other to effect change in antimalarial treatment policy. Hence we conclude that CQ can no more be solely relied upon for the treatment of falciparum malaria in Osogbo, Nigeria. AQ+SP and CH+CQ are effective in the treatment of acute uncomplicated malaria and may be considered as useful alternative drugs in the absence of artemisinin-based combination therapies.

Chlorpheniramine impairs spatial choice learning in telencephalon-ablated fish

This work investigated the effect of the Hj receptor blockade in the forebrain of ablated Carassius auratus in a simple stimulus-response learning task using a T-maze test with positive reinforcement. The goldfish were submitted to surgery for removal of both telencephalic lobes five days before beginning the experiment. A T-shaped glass aquarium was employed, with two feeders located at the extremities of the long arm. One of the two feeders was blocked. The experimental triáis were performed in nine consecutive days. Each fish was individually placed in the short arm and confined there for thirty seconds, then it was allowed to swim through the aquarium to search for food for ten minutes (máximum period). Time to find food was analysed in seconds. Animáis were injected intraperitoneally with chlorpheniramine (CPA) at 16 mg/kg of body weight or saline after every trial, ten minutes after being placed back in the home aquarium. The results show that all the training latencies of the A-SAL group were higher than the latencies of the S-SAL group. The S-SAL group had decreased latencies from the second trial on, while the S-CPA group showed decreased latencies after the fourth trial. The A-SAL group showed reduced latencies after the fifth trial, but the A-CPA group mainteined the latencies throughout the experiment. This suggests that CPA impairs the consolidation of learning both on telencephalon ablated animáis and in sham-operated ones through its action on mesencephalic structures of the brain and/or on the cerebellum in teleost fish.

Parotiditis crónica recidivante con trastornos inmunológicos asociados / Parotiditis chronic recidivante with immune inconveniences associates

En el departamento de ultrasonido diagnóstico fue atendida una paciente, de tres años de edad, que presentaba inflamación de ambas glándulas parótidas y que había presentado varios episodios de dolor, tumefacción unilateral o bilateral y fiebre. Había sido valorada en varias ocasiones por pediatría y había recibido múltiples tratamientos con antibióticos. Se le indicó ultrasonido de partes blandas y se valoró por inmunología. Se encontró un retardo en la fagocitosis y una disminución de la inmunidad celular. Se puso tratamiento con inmunomoduladores y antihistamínicos.

A 3-year-old female patient with swelling of both parotid glands that had presented various episodes of pain, unilateral or bilateral tumefaction and fever was seen at the diagnostic ultrasound department. She had been evaluated on several occasions by the pediatric department and had received multiple treatments with antibiotics. An ultrasound of soft tissues was indicated and she was assessed at the immunology service. A phagocytosis retardation and a reduction of cellular immunity were found. A treatment with immunomodulators and antihistamines was applied.

Descrição de um surto de lepidopterismo (dermatite associada ao contato com mariposas) entre marinheiros, ocorrido em Salvador, Estado da Bahia / Description of an outbreak of lepidopterism (dermatitis associated with contact with moths) among sailors in Salvador, State of Bahia

A ocorrência uma dermatite pápulo-pruriginosa em toda a tripulação de um navio comercial filipino em Salvador, BA, foi associada ao contato com mariposas do gênero Hylesia. Esta enfermidade insólita é causada por cerdas corporais das mariposas (flechettes). O relato dos casos serve como alerta para possíveis situações semelhantes.

An occurrence of pruritic papular dermatitis among the whole crew of a Filipino commercial ship in Salvador, State of Bahia, was associated with contact with Hylesia moths. This unusual type of dermatitis is caused by the bristles (flechettes) on the moths' bodies. Reporting on such cases serves to warn about possible similar situations.

Enhancement of the antimalarial efficacy of amodiaquine by chlorpheniramine in vivo

Resistance in Plasmodium falciparum to amodiaquine (AQ) can be reversed in vitro with with antihistaminic and tricyclic antidepressant compounds, but its significance in vivo is unclear. The present report presents the enhancement of the antimalarial efficacy of AQ by chlorpheniramine, an H1 receptor antagonist that reverses chloroquine (CQ) resistance in vitro and enhances its efficacy in vivo, in five children who failed CQ and/or AQ treatment, and who were subsequently retreated and cured with a combination of AQ plus CP, despite the fact that parasites infecting the children harboured mutant pfcrtT76 and pfmdr1Y86 alleles associated with AQ resistance. This suggests a potential clinical appliation of the reversal phenomenon.

Effects of pyrimethamine-sulphadoxine, chloroquine plus chlorpheniramine, and amodiaquine plus pyrimethamine-sulphadoxine on gametocytes during and after treatment of acute, uncomplicated malaria in children

The effects of pyrimethamine-sulphadoxine (PS), chloroquine plus chlorpheniramine, a H1 receptor antagonist that reverses chloroquine resistance in Plasmodium falciparum in vitro and in vivo (CQCP), and amodiaquine plus pyrimethamine-sulphadoxine (AQPS) on gametocyte production were evaluated in 157 children with acute, symptomatic, uncomplicated falciparum malaria who were treated with these drugs. PS was significantly less effective than CQCP or AQPS at clearing asexual parasitaemia or other symptoms of malaria. Gametocyte carriage on days 3, 7, and 14 were significantly higher in those treated with PS. The ratio of the density (per æl blood) of peripheral young gametocyte (PYG), that is, < stage III to peripheral mature gametocyte (PMG), that is, stage IV and V, an index of continuing generation of gametocytes, rose to 1 by day 7 of treatment in those treated with PS, but remained consistently below 1 in the other treatment groups. PYG-PMG density ratio increased significantly from day 0-14 in those treated with PS and CQCP (chi2 = 76, P = 0.000001 and chi2 = 42.2, P = 0.00001, respectively) but decreased significantly in those treated with AQPS (chi2 = 53.2, P = 0.000001). Both PS-sensitive and -resistant infections generated PYG (18 of 29 vs 13 of 20, chi2 = 0.04, P = 0.93) but PYG was present only in those with resistant response to CQCP. Combination of PS with amodiaquine (AQ), that is, (AQPS) resulted in less production of PYG, but in this setting, PYG was not indicative of response to AQPS. These data indicate that PS enhanced production or release of young gametocytes when used alone, but generated less young gametocytes when used in combination with AQ. PYG may be used as an indicator of response to CQCP but not PS or PS-based combination drugs.

Liquen simple crónico vulvar unilateral / Lichen simplex chronicus

Presentamos un caso de liquen simple crónico vulvar izquierdo, en una paciente con diagnóstico psiquiátrico de trastorno bipolar, tratado repetidamente como micosis. Se realizó biopsia que confirmó el diagnóstico y se trató exitosamente con antihistamínicos orales y corticoides tópicos.