Proceedings of the Western Pharmacology Society最新文献

Estrogens are fundamental to maintaining bone mineral balance. 17beta-aminoestrogens produce low estrogenic effects through ERalpha and ERbeta receptors, however their effects on bone tissue are unknown. This work evaluates the effects of the 17beta-aminoestrogen pentolame (AEP) and estradiol (E2) on the mineral profile of rat femur. Six months after ovariectomy (Ovx) adult Wistar rats (200-250g) were treated every third day for 30 days with subcutaneous (s.c.) injections of E2 (1, 10, 100 microg/kg), AEP (1, 10, 100, 500 microg/kg) or vehicle (propylenglycol; 1 ml/kg). After treatment, femur samples were prepared and Ca, P, Mg, Si, Fe, S, Na, K, and Cl concentration profiles were estimated using an X-ray analysis system coupled to an scanning electron microscope. Ovariectomy significantly decreased Ca, P, Mg and Si and increased Fe and S. Treatment with E2 restored Ca, P, Mg, and Si to the control values and decreased Fe and S in a dose dependent manner. AEP restored the levels of Ca, P, Mg and Si at all doses administered. AEP increased the levels of Fe and restored S to the basal level. The other minerals showed great variability and no significant differences were detected. Our results indicate differential action of AEP related to E2 in the restitution of bone mineral content.

Guaiacol is a compound used as expectorant. In Mexico City, this product is being illegally used for aesthetic treatment with fatal results. The aim of this study is to confirm the lethal toxicity documented in humans. Male Swiss Webster mice (CFW) 30-45g were employed. Dose-response curves to guaiacol were performed by subcutaneous administration (6.25-400 microl/40g). Basal temperature was recorded 30-120 min following administration of guaiacol. Animals were continuously observed for 120 min after guaiacol administration, lethality and toxicity manifestations were recorded. Depending of the dose, high toxicity was observed; sub lethal doses (6.25-12.5 microl/40 g) produced tachycardia and hyperactivity, follow by sedation, hypnosis, high hypothermic effect (loss of 6 degrees C) dyspnea, myoclonus, hematuria, blindness, abdominal distension and in higher doses (25-400 microl/40 g) lethal effect. Necropsy showed hepatic and renal necrosis, pulmonary edema, hemorrhages and bladder clotting. We concluded that guaiacol is an extremely toxic product (toxic rating class 5) whose use should be restricted or banned.

The purpose of the study was to identify the level of knowledge of local anesthetics frequently used in the surgical clinic by third and fourth year dental students in daily practice. The importance of pharmacology in dental practice in underscored by potential drug toxicity. The study was performed with 244 third and fourth grade career dental students (CDS). Eleven items regarding the knowledge over local anesthetics at the clinic; i.e., the appropriate doses, possible toxic effects and side effects were examined. The reference questionnaire which is in a validation process, is a way to evaluate student knowledge about most drugs used in odontology practice such as: NSAIDs, antibiotics and local anesthetics. The results were found to be unsatisfactory with a high percentage of students failing (less than six of eleven items correct). We conclude that determination of practice knowledge is an essential step in informing the institution about cognitive deficiencies identified in order to plan learning solutions.

Information overload, proliferation of new drugs and curricular reforms have been recognized as three of the major factors contributing to the insufficient pharmacological education of medical students. To remedy this situation, it has been recommended that a curriculum more selective in knowledge content coupled with a restricted list of drugs be developed. Based on our own teaching experience, common educational objectives, competencies to be achieved, profiles of morbidity and mortality of the Mexican population, and knowledge of the literature, we have identified what should constitute the core content of pharmacology courses in medical schools. Selected themes were grouped in three categories and the number of drugs that undergraduate medical students have to manage is limited to 139. We have developed a concrete, medicine-focused, core pharmacology program dealing with themes and drugs that will best constitute the primary teaching/learning material for undergraduate medical students.

The aim of this study was to evaluate the analgesic efficacy, safety, opioid sparing effects and improvement of respiratory function when using 0.2% ropivacaine continuous wound infiltration after major intra-abdominal surgery. Forty patients undergoing major intra-abdominal surgery requiring a midline incision of > or = 20 cm were enrolled into this IRB-approved, randomized, prospective controlled study. Group 1: 20 patients, parenteral analgesia (control group). Group II: 20 patients, with local anesthetic wound infiltration (pain pump group). At the end of the procedure, in the pain pump group of patients, a multi hole, 20-gauge catheter was inserted percutaneously, above the fascia. An initial dose of 10 ml of 0.2% ropivacaine was injected in the wound through the catheter. A device provided continuous delivery of 0.2% ropivacaine; the infusion was initiated at 6 ml/h for the following two days. The total "rescue" morphine and oxycodone/acetaminophen tablets administered were significantly lower in the pain pump group. At all time intervals, resting pain scores were significantly lower in the pain pump group when compared with the control group. However, at the 4-48 and 12-48 hours pain scores generated after leg raise and coughing, respectively, were significantly lower in group II. The patient vital capacities were insignificantly higher in group II. We conclude that after major abdominal surgery, infiltration and continuous wound instillation with 0.2% ropivacaine decreases postoperative pain, opioid requirements and oral analgesia. Early patient rehabilitation, hastening convalescence, and preventing respiratory complications are expected outcomes of this approach.

The administration of fibrinolytic agents in the pleural cavity is an alternative treatment for the management of loculated empyemas in patients who are poor candidates for surgery and/or do not respond to more standard treatments (e.g., chest tube placement, pleurodesis). Unfortunately, in practice it is not frequently offered as an alternative treatment approach. Here we present the case of a 79-year-old male with right lower lobe pneumonia complicated by a parapneumonic pleural effusion that showed minimal improvement after chest tube placement and broad-spectrum antibiotic treatment. Intrapleural tissue plasminogen activator (tPA) was administered daily for three consecutive days, which resulted in the breakdown of intrapleural loculations and facilitation of drainage, followed by significant clinical and radiologic improvement. tPA was successful in the treatment of parapneumonic pleural effusions in a patient who was not a candidatefor surgical intervention and who failed to respond to standard treatments.

We have compared the frequency and types of cancer chemotherapies used in a private hospital and in a government-based hospital in Mexico City. A retrospective study was conducted from January 2005 to December 2007, and therapeutic management determined in 415 cases reviewed by the attending physicians of the oncology service. In the government-based hospital, 60 different types of cancer were found among 273 patients diagnosed. Acute lymphoblastic leukemia (ALL) had the greatest incidence (30%), followed by Hodgkin's lymphoma (9%), retinoblastoma (7%), neuroblastoma (6%), and osteosarcoma (6%). The entire number of chemotherapy sessions was 7575. Drugs most frequently employed included etoposide (577), followed by methotrexate (575), vincristine (483), cyclophosphamide (312), and cytarabine (277). The economic status among these patients was mainly of limited resources and represented 80% of the total number of patients. The types of cancer found in the private hospital were similar, however the drugs used were predominantly cyclophosphamide (416), doxorubicin (382), 5-fluorouracil (368), paclitaxel (237) and cisplatin (128). The types of cancer were similar in both hospitals and reflected the incidence among the entire population in Mexico, since acute lymphoblastic leukemia, Hodgkin's lymphoma and retinoblastoma, were the types most represented. However, the treatment schemes differed; the chemotherapeutic agents used in the private hospital were rather more specific but significantly more expensive than those employed in the government hospital.

Development of atypical antipsychotic compounds is an important task in pharmacology in order to improve therapeutic features and avoid side effects shown by classical antipsychotic compounds. The prototype of the second generation compounds, clozapine differs from typical antipsychotics by having a high D4 and 5HT(2A) and low D2 receptor affinity. Clozapine is the prototype agent for screening new atypical antipsychotic compounds. Clozapine was compared to haloperidol in the open field animal model in which crossings, rearings and rearing time were analyzed. Clozapine (0.5 and 1 mg/kg) and haloperidol (0.03 mg/kg) were administered by intraperitoneal injection. Five days before experiments, animals were given methylphenidate (12 mg/kg, orally). The experiments were performed 24 hr after the last methylphenidate dose. In the open field test, clozapine blocked the increase in rearing time and rearings elicited by methylphenidate administration in a dose-dependent fashion. No effect was observed in crossings at 1 mg/kg, but there was at 0.5 mg/kg. This could be related to an anxiolytic action at this dose. Haloperidol blocked the increase in rearing time, rearings and crossings. Results are discussed in terms of the putative participation of D4 subtype receptors in the mediation of time and rearing behavior. This approach could be used for the screening of atypical antipsychotic drugs.

The blockade of renin-angiotensin system by pharmacological interventions with angiotensin converting-enzyme (ACE) inhibitors or AT1 receptor antagonists in the juvenile critical age may attenuate or even prevent the development of hypertension. In this work, we determined the Ang II type 1 (AT1) receptor role in L-NAME-induced hypertension in pithed rats. Male Wistar rats (250-300 g) were used. Rats were divided into the following groups: Control (tap water) and N(omega)-Nitro-L-arginine methyl ester (L-NAME, 60 mg/kg/day/2 weeks). Dose-response curves to Ang II were constructed in the pithed rat. The results show that Ang II evoked blood pressure increase in pithed rats in a dose-related manner. In L-NAME-treated rats a greater maximal effect was observed, indicating that L-NAME promotes Ang II hypersensitivity. In L-NAME-treated rats, Ang II response was blocked by losartan (1 and 3 mg/kg), a selective AT1 receptor antagonist, indicating that AT1 receptor influence L-NAME hypertensive mechanism. Our results suggest that Ang II hypersensitivity in L-NAME-induced hypertension can be due to increased AT1 receptor expression or sensitivity changes.

Human breast cancers metastasize early in tumorigenesis and distant lesions, though dormant are very likely extant at the time of diagnosis and treatment in the majority of cases. Removal of primary tumors by surgeons as an imperative of the current treatment approach, also removes inhibitory factors secreted by the primary tumor that had maintained the dormancy of the metastases. We have identified a factor secreted by human breast cancer cells that supports the formation of blood vessels and may be a principal early factor supporting the growth and development of metastases in human disease. Here we demonstrate for the first time that this factor, secreted (s) human (h) nucleoside diphosphate kinase type B (shNDPK-B), product of the nm23-h2 gene, can be detected specifically with high sensitivity (50 pg/ml; 2.5 pM) in an ELISA assay of our own design. We further demonstrate that shNDPK-B is released into the circulation in immunocompromized mice carrying the human breast carcinoma cell MDA-MB-231. These data support the hypothesis that shNDPK-B may be responsible for the early events in angiogenesis supporting both primary and metastatic tumor growth and development.