Proceedings of the Western Pharmacology Society最新文献

Midazolam (MDZ) administered during the neonatal period induces histological changes in the cerebellar cortex of mouse pups. We investigated whether these changes are similar to those induced by prenatal exposure to diazepam (DZ). Two neonatal ICR-strain mouse groups were injected daily from day 8 to 29. The first group (MDZ) was treated with a single daily MDZ dose (2.0 mg/kg/body weight) and the second with saline solution. The mice (10 MDZ and 10 control), were sacrificed in a CO2 atmosphere at 30 days; the cerebellum was fixed in 2.5% glutaraldehyde, post-fixed in 1% OsO4 and embedded in epoxy resin. Semifine sections were stained with toluidine blue and observed under a light microscope. The cerebellar cortex of the MDZ group was thinner than that of controls. The cortex showed a reduced number of Purkinje cells, some with a shrunken cytoplasm and degenerative signs. The dendrite tree was swollen with disoriented branches. Numerous granular cells remained in the molecular layer with few in the granular layer (p<0.05). The nucleus of Purkinje cells and granular cells showed atypical heterochromatin distribution, irregular nuclear surface, and voluminous nucleoli. The neuropile and myelin fibers showed delayed differentiation. Postnatal exposure to MDZ produces similar histological changes in the cerebellar cortex of the 30-day-old mouse treated for 21 days, to those induced by prenatal exposure to DZ.

Splenic lymphoma, or primary malignant lymphoma of the spleen (PMLS), is an uncommon condition whose true nature is difficult to define due to the variable ways it has been classified. Out of all non-Hodgkin's lymphomas it comprises less than 2% of cases. Some experts suggest that PMLS only involves the spleen and splenic hilum, while others consider PMLS to be an entity that develops within the spleen and later has the potential for invading adjacent organs and metastasizing. Clinical features of splenic lymphoma are characterized by nonspecific systemic symptoms such as low grade fevers, night sweats and symptoms related to considerable splenomegaly. Most of these lymphomas are of B-cell origin showing low or intermediate-grade lymphoma on histological analysis. The case we present here is of a patient presenting with left sided flank pain, and given a previous history of nephrolithiasis, a presumably simple diagnosis of kidney stones was made. However, further investigation led to the discovery of splenic lymphoma, which was asymptomatic earlier but may have manifested symptoms that mimicked renal colic.

Nimesulide is a non-steroidal anti-inflammatory agent that is widely used in the treatment of inflammatory pain. The drug belongs to the class II of Biopharmaceutical Classification System (low solubility, high permeability) and therefore, absorption of this drug is limited by its dissolution. It has been established that complex formation of insoluble substances with cyclodextrins may increase their oral bioavailability since solubility is improved. In order to provide test this hypothesis, a comparison on the oral pharmacokinetics of two suspensions of nimesulide in rats was carried out. Two groups of 7 rats were employed. One group received an oral dose of 10 mg/kg of a suspension prepared with 0.5% carboxymethylcellulose solution in water, whereas the other group received a commercially available formulation containing the complex of nimesulde-beta cyclodextrins (Eskaflam). Blood samples were obtained at selected times for a period of 12 hours and analyzed by an HPLC method. Pharmacokinetic parameters obtained were as follows: Cmax 1.18 +/- 0.16 and 1.93 +/- 0.12 microg/ml, tmax 5.25 +/- 1.03 and 3.21 +/- 0.91 h and AUC 8.65 +/- 1.19 and 13.74 +/- 0.70 microg hr/ml for carboxy-methylcellulose and Eskaflam, respectively. Values for Cmax and AUC12hr were increased and a reduction of tmax was observed indicating improved absorption of nimesulide in the formulation containing beta-cyclodextrins.

Heptachlor has been widely used as an insecticide. It is a GABA-A antagonist and causes seizures. It also increases peripheral benzodiazepine receptors (PBRs) in brain. PBRs are found on the outer mitochondrial membrane in glia, rather than in neurons, and are necessary for steroidogenesis in brain. We compared the effects of acute oral administration of heptachlor (60 mg/ml oil/kg body wt) at 10 ages from postnatal day (PND) 0 to 60 on brain PBR expression and seizure severity in both male and female rats at 1 and 2 hr after administration. From PND 10 through 60, brain PBR expression was increased about 175-225% of controls at both 1 and 2 hr after heptachlor in females. In males however, PBRs were only increased at 30-60 days at 1 hr but not at any age at 2 hr. At 2 hr after heptachlor at 30-60 days in males, PBRs were significantly lower than at 1 hr and even tended to be lower than control levels. By contrast, seizure intensity was greater in males than in females from 10 through 20 days of age at 1 hr and was even greater at 2 hr from 16 through 30 days of age, reflecting the lower PBR levels at 2 hr than at 1 hr in males. Thus, the gender difference in PBR expression was the opposite of the gender difference in seizure intensity. PBRs in brain synthesize several neurosteroids, including allopregnanolone, which is a potent anticonvulsant agent. We hypothesize that the gender differences in seizure intensity after heptachlor were due to the action of heptachlor in greatly increasing PBR expression in females but not in males. Thus the greater expression of PBRs in females would result in more synthesis of allopregnanolone than in males. Therefore, because of allopregnanolone's anticonvulsant effects, seizure intensity was less in females than in males. By comparison, maximal electroshock (MES) caused seizures and increased PBRs in brain in both male and female developing rats with no gender differences at 10-20 days of age.

Diastolic dysfunction (DD) is a common entity associated with advanced age and hypertension, often present in patients with ischemic heart disease. The correlation of DD and coronary artery disease (CAD) in asymptomatic young patients is not known. We sought to determine the prevalence of CAD risk factors in asymptomatic patients with DD. We present data from a retrospective chart review of CAD risk factors in asymptomatic patients diagnosed with DD during an echocardiograph examination. We screened all patients that had an echocardiographic examination at Lenox Hill Hospital from January 2004 until July 2007. DD was diagnosed if an impaired filling pattern with an E/A ratio less than one was noted on the mitral inflow pulse wave doppler. One-hundred and one patients met study criteria. Data regarding the presence of the following risk factors was collected: sex, hypertension, hyperlipidemia, smoking, diabetes, peripheral artery disease, and family history of CAD. The mean age of patients was 48 +/- 6; 50% were male. The most prevalent CAD risk factor in this group of patients with DD was hypertension (53%), followed by hyperlipidemia (31%) and diabetes (22%). These data can help identify those patients who are asymptomatic in terms of DD who may be at risk for the condition. These patients should undergo an echocardiograph examination in order to rule out presence of DD, even if symptoms are not present.

We present the unique case of an eighty-nine-year-old male without any immunodeficiency state or taking immunosuppressive medication and who did not have conditions affecting clearance of the esophageal lumen who was diagnosed with simultaneous herpetic esophagitis and candidal duodenitis.

The role of cGMP in the myometrium of pregnant women is not completely known. We have previously shown in guinea pig, monkey and man that NO-induced relaxation of oxytocin-induced contractions is independent of cGMP accumulation. To approach an understanding of the role of cGMP in myometrium, we have developed smooth muscle cell cultures from pregnant women undergoing caesarian section at term. Cells, grown in standard media containing progesterone, express smooth muscle cell markers and are used within five doublings. Cells stimulated with NO donors increase their cGMP levels nearly 100 fold (basal = approximately 9 pmol/mg protein). In the presence of oxytocin (OT; 1 microM), cGMP accumulation in the presence of NO (100 microM) is significantly blunted (25 fold). Cyclic GMP-degradation is inhibited by the presence of the phosphodiesterase inhibitor zaprinast; suggesting that the ability of OT to attenuate cGMP accumulation is unlikely to be due to degradation. We propose that the elevation of intracellular calcium following the addition of OT suppress the activity of a calcium-sensitive guanylyl cyclase. The diminution of cGMP synthetic potential in myometrial cells from pregnant women is consistent with the absence of a role for cGMP in the NO-induced relaxation of uterine muscle.

Nutritional support is a critical step in caring for hospitalized patients both to avoid possible metabolic alterations that would worsen the patient's condition, or as a direct result of a particular disease. The purpose of the present study was to describe a procedure for the prescription of total parenteral nutrition (TPN), its administration, monitoring and the complications experienced in a third level hospital in Mexico, as applied to pediatric and adult patients given TPN. The study was carried out for a period of 30 months. TPN was prescribed according to the clinical status of patients. The study reviewed 4,000 parenteral nutrition records from January 2005 to June 2007 (30 months). Based on data here presented a guideline was applied to improve the nutritional support of patients as part of the need to ensure their recuperation during their hospitalization. We observed that TPN must be individualized, based on daily nutrient recommendations, which can be useful to assess the nutritional status of the hospitalized patient with diverse pathologies.

Global climate change is one of the instigating and contributing factors for epidemic outbreaks of infectious diseases in human populations. In the years 2003 to 2005 the city of Tampico, in the northern state of Tamaulipas, Mexico, experienced recurrent outbreaks of dengue virus infections (DV) and the resulting dengue fever (DF). One of the hallmark symptoms of DF, which appears to worsen as the environmental temperature increases, is thrombocytopenia. In as much as it is a hallmark for hemorrhagic manifestations, thrombocytopenia is a useful sign to monitor the course of infected patients. Extracellular calcium (Ca2+ o) plays a key role in blood clotting; its chelation in vitro with ethylenediaminetetracetic acid (EDTA) or citrate prevents clotting, while exogenous recalcification of plasma leads to shortening of clotting time. In vivo, Ca2+ o is essential for platelet function and for the regulation of the immune response. In this work we report a significant increase (p<0.05) in the number of blood platelets of patients with clinical signs and symptoms of DF following oral administration of calcium carbonate (CAL, 1.2 to 1.8 g/day; n=10) when compared with a control group (CTL, n=10): 89 (46-132) versus 206 (155-257). Data expressed as mean value (95% confidence interval, C.I.) for x1000 cells/mm3. CAL also improved overall clinical condition and reduced by 36 % the duration of signs and symptoms of DF: 6.7-11.3 days, versus 11.5-16.6 days (95 % C.I., p<0.05) when compared with CTL patients. The possible mechanism of calcium attenuated thrombocytopenia and clinical improvement is discussed.

Takotsubo cardiomyopathy, also known as stress induced cardiomyopathy and transient left ventricular apical ballooning syndrome, is a rare syndrome that is characterized by a transient decrease in ejection fraction. This is accompanied by hypokinesis of the left ventricle and ballooning of the apex, with hypercontractile base and non-obstructive coronary artery disease. Takotsubo was first described in Japan in the early 1990's. It was named such due to the morphology of the apical ballooning that is similar in shape to a 'takotsubo', which is a pot with a round bottom and narrow neck used for trapping octopuses. Though most often described in Asians, reports of Takotsubo in Caucasian populations is becoming more common, possibly due to heightened awareness and detection. The most common presenting symptom of Takotsubo is acute chest pain mimicking myocardial infarction. Patients may also present with dyspnea, pulmonary edema and, more rarely, cardiogenic shock. Clinical symptoms are accompanied by transient left ventricular dysfunction. Despite clinical symptoms consistent with acute myocardial infarction, normal coronary arteries are usually detected upon cardiac catheterization. The case presented here is of an Asian woman who developed symptoms of acute myocardial infarction during a stressful hospital stay.