Search

Chronic renal failure requiring dialysis or transplantation is known as end-stage renal disease. Several drugs are used to treating the symptoms, co-morbid conditions and treatment side effects of end-stage renal disease. We investigated drug treatment during the period of hemodialysis in children with end-stage renal disease in the Hospital del Niño DIF, Pachuca, Hidalgo, Mexico. Data were collected from hospital records. The data included demographic, clinical data and those on drug usage. A total of 13 patients were included. The average age of patients was 14.2 +/- 2.1 years. Eighteen different medications were administered; the mean number of drugs during the period of hemodialysis was 1.3 +/- 0.6 (range 1-4). Two-hundred sixteen doses of medication were administered in 130 hemodialysis sessions. The drugs most used were erythropoietin (42.7 %), followed by dextrose solution (18.9 %), calcium gluconate (10.4 %), iron dextran (9.1%) and nifedipine (5.5 %). Medications may be used to help control some of the issues associated with kidney failure or hemodialysis. Our study showed that few drugs are administered to children with ESRD during their period of hemodialysis.

Aloysia triphylla is traditionally utilized for the treatment of menstrual colic (primary dysmenorrhea) in Mexico. Citral is the main chemical component found in Aloysia triphylla leaves extract. Primary dysmenorrhea is a very frequent gynecological disorder in menstruating women, affecting 30-60% of them. It is usually treated with non-steroidal anti-inflammatory drugs (NSAIDs); although their effect is rapid, they possess many side effects. Due to these shortcomings, Mexican folk therapy is considered as a feasible alternative. The effects of the hexane extract of Aloysia triphylla and citral on uterine contractions were evaluated in vitro as well as their anti-inflammatory properties and gastric wound capabilities were assessed in vivo. The inhibitory effects on the contractions were analyzed using isolated uterus strips from estrogen primed rats. Contractions were induced by KCl 60 mM, oxytocin 10 mIU/mL, charbacol 10 µM and PGF(2α) 5 µM. The anti-inflammatory effect was assessed on carrageenan-induced rat hind paw edema model. The inhibitory concentration-50 (IC(50)) of the hexane extract of Aloysia triphylla upon each contractile response was for KCl 44.73 ± 2.48 µg/mL, oxytocin 42.16 ± 3.81 µg/mL, charbacol 41.87 ± 1.73 µg/mL and PGF(2α) 28.70 ± 2.40 µg/mL in a concentration-dependent way. The extract of Aloysia triphylla produced a significant inhibitory effect on PGF(2α)-induced contraction compared to its inhibitory actions on the others. Citral exhibited the same inhibitory effect on the contraction induced by PGF(2α). The oral administration of the extract (100-800 mg/kg) and citral (100-800 mg/kg) showed anti-inflammatory activity; furthermore, the maximal dose utilized did not produce gastric injury. These results were compared with anti-inflammatory effects and gastric damage produced by 30 mg/kg of indomethacin p.o. The spasmolytic and anti-inflammatory effects support the traditional use of Aloysia triphylla leaves in the treatment of the primary dysmenorrhea in Mexican communities.

Pharmacovigilance is the permanent collection and assessment of the safety data of drugs in the interest of precise knowledge of the safety profile. We monitored notifications of suspected adverse reactions (AR) produced by psychoactive medications (ARPM) in a Psychiatry Hospital, during a 4-month period. Yellow cards for adverse reaction reporting were distributed to the medical personal at the Hospital Psiquiátrico Villa Ocaranza, Pachuca Hidalgo, Mexico. For each notification, the ARPM was analyzed in order to verify causality. One hundred twelve hospitalized patients entered the study (44 male and 68 female). The mean +/- SD age of the patients was 46 +/- 4.5 years. The major diagnoses found were: schizophrenia (35.7%), severe mental retardation (17 %), moderate mental retardation (MMR)/epilepsy (12.5%), MMR (8.03%), and others (26.7%). During the study there were 721 therapeutic regimens prescribed to patients on psychiatric service. Patients were receiving an average of 5.3 +/- 1.1 (range 4 to 8) psychiatric medications. The psychiatrists reported only 5 ARPMs in five patients (prevalence: 4.46%). Among the drugs involved were neuroleptics (47.8%), antiepileptic (39.1%), and others (13.04%). The organs and systems affected by the ARs were the central nervous system, skin, endocrinological and gastrointestinal. A causal association between the medication and the AR were classified as probable in three cases, as possible in one case, as doubtful in one case and as definite in no case.

Tissue degeneration, infection, inflammation, cancer, trauma, surgery and limb fractures all produce pain. Each of these physiological abnormalities requires a therapeutic approach different from the last. In acute pain, caused by fracture, several classes of analgesics have been utilized. These basic remedies for analgesia, however, are still confined to a small number of medications, including nonsteroidal anti-inflammatory drugs (NSAIDs), local anesthetics and opioids. In addition, most of these drugs have side effects, limiting their use in clinical practice. The purpose of this study was to compare the efficacy of three NSAIDs to relief acute pain caused by ankle fracture. Sixty subjects with ankle fracture were randomized to receive ketorolac, diclofenac, or etoricoxib, every 12 hours in a prospective, double-blind study. Forty-nine patients completed the study. The subjects' assessments of ankle pain on the visual analog scale and a Likert scale showed a significant reduction from baseline over 24 hr, regardless the treatment group. All treatments showed a similar profile in pain reduction. Etoricoxib, diclofenac and ketorolac twice daily are a rapid and effective treatment for acute pain. All the regimens were well tolerated in this study.

Several species of the South American genus Akodon present fully fertile XY females besides XX ones. To analyze the possibility of a Sry mutation as the cause of sex reversal in A. azarae and A. boliviensis, we determined the sequence of the Sry gene in 2 males and 3 XY females from each of these species. The Sry gene sequence was also studied in A. dolores, a species that does not have XY females. In inter-specific comparisons, the percentage identities with respect to the region analyzed varied between 96.8% and 97.9%. An ORF of 543 nucleotides was identified, and the predicted Sry proteins comprised 180 amino acids, with an HMG domain of 83 amino acids. Our results indicate that female sex reversal in A. azarae and A. boliviensis cannot be explained by sequence differences in the Sry region analyzed here, which includes the complete ORF and, together with previous results concerning the inheritance of the XY condition, show that Sry mutation is not the basis of sex reversal., (Copyright 2010 S. Karger AG, Basel.)

Objective: To evaluate factors affecting the prevalence of dysmenorrhea in a group of Mexican students., Method: A questionnaire was administered to 1152 high school students and the obtained data about severity, symptoms, and medications used were analyzed., Results: Dysmenorrhea had a prevalence of 48.4% and was the cause of school absences for 24% of the affected students. It was mild in 32.9%, moderate in 49.7%, and severe in 17.4% of these students, of whom 28% consulted a physician and 60.9% self-medicated. The most common over-the-counter drugs used were a combination of paracetamol, pamabrom and pyrilamine maleate; metamizol (a nonsteroidal anti-inflammatory drug) plus butylhioscine; and naproxen. We found a significant correlation between the presence of dysmenorrhea and smoking, cycle pattern, cycle duration, flow duration, and amount of flow., Conclusion: The prevalence of dysmenorrhea was high in our sample. The condition caused short-term school absences and the students commonly addressed it by self-medicating.

Aromadendranes belong to a class of sesquiterpenes present in higher plant essential oils and marine animals. Although the biological activities include antifungal, antibacterial, antiviral, plant growth regulatory, antifeedant, repellent and cytotoxic, there is only one precedent for spasmolytic effects. In a previous report we have shown that the aromadendrene molecule known as spathulenol, isolated from Lepechinia caulescens, efficiently relaxes rat uterus rings and therefore in the present work we describe structure-activity relationships of thirteen aromadendranes, most of them having the trans-fused perhydroazulene skeleton, with spasmolytic activity.

Heliopsis longipes is an herbaceous plant found in Mexico, used traditionally for its analgesic and anesthetic activities. Plant extracts in combined use with synthetic drugs may represent a therapeutic advantage for the clinical treatment of pain, allowing the use of lower doses, and limiting side-effects. Therefore, the main objective of this study was to determine the possible pharmacological interaction between Heliopsis longipes ethanolic extract (HLEE) and diclofenac in the Hargreaves model of thermal hyperalgesia in the mouse. HLEE, diclofenac or fixed-dose ratio HLEE-diclofenac combinations were administered systemically to mice and the antihyperalgesic effect was evaluated using the thermal hyperalgesia test. All treatments produced a dose-dependent antihyperalgesic effect. ED(30) values were estimated for all the treatments and an isobologram was constructed. The derived theoretical ED(30) value for the HLEE-diclofenac combination was 54.4+/-9.4 mg/kg body wt, significantly higher than the actually observed experimental ED(30) value, 8.6+/-4.0 mg/kg body wt. This result corresponds to synergistic interaction between HLEE and diclofenac in the Hargreaves model of thermal hyperalgesia. Data suggest that low doses of the HLEE-diclofenac combination can interact synergistically at the systemic level and that this association may therefore represent a therapeutic advantage for the clinical treatment of inflammatory pain.

A novel topical ophthalmic formulation of the preferential COX-2 inhibitor meloxicam has recently been developed. The purpose of the present study was to evaluate the efficacy and safety of this novel 0.03% meloxicam solution with regard to a reference 0.1% diclofenac formulation in a prospective, parallel, randomized, multicenter, double-blind study. Two groups of patients submitted to phacoemulsification with intraocular lens implantation were formed. Patients in one group were treated with meloxicam and those in the other group with diclofenac. Dosing was 1 drop t.i.d. for 30 days, beginning the first day after surgery, for both treatments. Inflammation was assessed by the presence of cells in the anterior chamber, anterior chamber flare, ciliary flush, photophobia and pain. Both treatments significantly reduced these indicators. Topical meloxicam and diclofenac produced a similar degree of burning sensation and conjunctival hyperemia. There was no significant difference between treatments in any of the measured parameters. It is concluded that the novel meloxicam solution is effective and safe. Meloxicam, however, did not offer any significant benefit over the diclofenac formulation in patients submitted to cataract surgery.

The main objective of the present study was to investigate the use of drugs in the pediatric intensive care units (PICUs) at a pediatric hospital. Data were equally collected from charts of PICUs of the Hospital del Niño DIF, Pachuca, Hidalgo, Mexico in 2007. The data included demographic, clinical data and those on drugs usage. A total of 45 patients were included at the study, all (100%) of whom received one or more drugs. Data were collected and 57 different drugs were given to the pediatric patients. The median number of drugs/inpatient was 6.9 (1-17). The therapeutic class most prescribed was anti- infective (30.6 % of all the prescriptions), followed by electrolytes (13.3 % of all the prescriptions) and gastrointestinal agents (12.9 % of all the prescriptions). KCI was the drug most commonly used (64.4 % of all the patients) followed by ranitidine and amikacin (both with 51.1 % of all the patients). As in many studies, the therapeutic class most used was the anti-infectives. Substantial variation exists in hospitalists' reported management of common pediatric conditions. To decrease undesirable variation in care, a stronger evidence base for inpatient pediatric care must be built.

Purpose: There is evidence that the sulfonylurea antidiabetic agent glibenclamide reduces the analgesic action of non-steroidal anti-inflammatory drugs (NSAIDs), opioids and neuromodulators in animal models. Therefore, in view of the vast clinical uses and interactions of NSAIDs with commonly used therapeutic agents, the interaction of the NSAID diclofenac and glibenclamide was investigated about pharmacokinetic profile and antinociceptive effect in rats., Methods: Antinociception was assessed using the formalin test. Fifty microliters of diluted formalin was injected s.c. into the dorsal surface of the right hind paw. Nociceptive behavior was quantified as the number of flinches of the injected paw during 60 min after injection. Rats were treated with oral administration of vehicle or increasing doses of diclofenac (3-18 mg/kg) before formalin injection. To determine the pharmacodynamic interaction between diclofenac and glibenclamide, the effect of oral administration of glibenclamide (1-30 mg/kg) on the antinociceptive effect induced by diclofenac (18 mg/kg, p.o.) was assessed. To evaluate the pharmacokinetic interaction between diclofenac and glibenclamide, the effect of glibenclamide (10 mg/kg, p.o.) on the pharmacokinetic of diclofenac (18 mg/kg, p.o.) was studied in the rat. Blood samples were taken over 8 h and analyzed using a validated high-performance liquid chromatography method to generate the pharmacokinetic profile of diclofenac. Pharmacokinetic parameters were estimated using noncompartmental analysis., Results: Systemic administration of diclofenac produced a dose-dependent antinociceptive effect in the formalin test. Systemic treatment with glibenclamide prevented diclofenac-induced antinociception. In pharmacokinetic interaction study, no significant (P>0.05) change in diclofenac concentration-time profiles in the presence of glibenclamide was detected., Conclusion: The experimental findings suggest that systemic glibenclamide is able to block the diclofenac-induced antinociception in the rat formalin test. Besides, this antagonism was not produced by diminution in the bioavailability of diclofenac. Likewise, the validated assay had sufficient accuracy and precision for pharmacokinetic determination of diclofenac in the rat.

Heliopsis longipes is an herbaceous plant found in Mexico. Heliopsis longipes is traditionally used for its analgesic and anesthetic properties. Plant extracts may represent a therapeutic advantage for the clinical treatment of pain. Therefore, the main objective of this study was to determine the possible antihyperalgesic effect produced by the Heliopsis longipes ethanolic extract (HLEE) in the Hargreaves model of thermal hyperalgesia in the mouse. HLEE was administrated systemically to mice and the antihyperalgesic effect was evaluated using the thermal hyperalgesia test. Oral Administration of HLEE produced a dose-dependent antihyperalgesic effect. Previously, it was reported that Heliopsis longipes extract was able to release GABA in mice temporal cortex slices. Therefore, it is likely that the antihyperalgesic effect observed in our study could result from GABA liberation and its inhibition of excessive excitation of nociceptive circuits in the thalamus and cortex evoked by tissue injury. Our results suggest that HLEE may represent a therapeutic advantage for the clinical treatment of inflammatory pain.

Background and Purpose: Acemetacin is a non-steroidal anti-inflammatory drug which is rapidly bioconverted to indomethacin, but produces significantly less gastric damage than indomethacin. This study was performed to investigate several possible mechanisms that could account for the gastrointestinal tolerability of acemetacin., Experimental Approach: The gastric and intestinal damaging effects of acemetacin and indomethacin were examined in the rat. Effects of the drugs on blood levels of leukotriene B(4) and thromboxane B(2), on leukocyte-endothelial adherence in post-capillary mesenteric venules, and on gastric expression of tumour necrosis factor-alpha (TNF-alpha) were determined. The two drugs were also compared for gastric toxicity in rats pretreated with inhibitors of COX-2 and NOS., Key Results: Acemetacin induced significantly less gastric and intestinal damage than indomethacin, despite markedly suppressing COX activity. Indomethacin, but not acemetacin, significantly increased leukocyte adherence within mesenteric venules, and gastric expression of TNF-alpha. Pretreatment with L-nitro-arginine methyl ester or lumiracoxib increased the severity of indomethacin-induced gastric damage, but this was not the case with acemetacin., Conclusions and Implications: The increased gastric and intestinal tolerability of acemetacin may be related to the lack of induction of leukocyte-endothelial adherence. This may be attributable to the reduced ability of acemetacin to elevate leukotriene-B(4) synthesis and TNF-alpha expression, compared to indomethacin, despite the fact that acemetacin is rapidly bioconverted to indomethacin after its absorption.

It has been proposed that the antinociception of systemic diclofenac is the outcome of peripheral and central actions. Hence, our purpose was to examine if systemic diclofenac is able to achieve effective concentrations at local and spinal sites and to characterize the interaction between its local and spinal actions. Pain was produced in the rat using the formalin test. Oral diclofenac (1-10 mg/kg) reduced formalin-induced pain. The antinociceptive effect of oral diclofenac (10 mg/kg) was abolished by local or spinal administration of either L-NAME (1-100 microg and 1-50 microg) or glibenclamide (12.5-100 microg and 25-75 microg). These results suggest that oral diclofenac achieves effective concentrations producing an antinociceptive effect involving participation of the NO-potassium channel pathway at both, the local and spinal levels. In an additional experimental series, diclofenac was administered either locally (25-200 microg) or spinally (12.5-100 microg), yielding an antinociceptive effect by both routes. Then, diclofenac was given simultaneously by these two routes in a fixed-ratio, and antinociception was assayed. Isobolographic analysis revealed an additive interaction between the local and spinal effects of diclofenac. Hence, our results provide evidence that the overall antinociceptive effect induced by systemic diclofenac is the outcome of central and peripheral mechanisms.

Hepatic glycogen metabolism is altered by nitric oxide (NO) during endotoxic shock. Thalidomide analogs immunomodulate the endotoxin-induced cytokines which regulate the NO release. We analyzed the short-term effects of some thalidomide analogs on the hepatic glycogen store and on the plasma and hepatic NO in an acute model of endotoxic challenge in rat. An endotoxin dose selection was performed. Rats received vehicle, thalidomide or analogs orally and, two hours after last dose, they were injected with endotoxin (5 mg/kg). Animals were sacrificed 2 h after challenge. Liver glycogen was quantified by the anthrone technique. Plasma and hepatic NO was determined by Griess reagent and HPLC. Hepatic interferon-gamma, a NO co-inducer, was measured by ELISA. Endotoxin caused inverse dose-dependent effects on plasma NO and on glycogen.Thalidomide analogs showed short-term regulatory effects on glycogen, some of them increased it. Plasma NO was almost unaffected by analogs but hepatic NO was strikingly modulated. Analogs slightly up-regulated the liver interferon-gamma and two of them increased it significantly. Thalidomide analogs may be used as a pharmacological tool due to their short-term regulatory effects on glycogen and NO during endotoxic shock. Drugs that increase glycogen may improve liver injury in early sepsis.

The bionomics of sand flies (Diptera: Phlebotominae) was studied monthly for two consecutive years in alluvial gallery forests in the department of Casanare, Northeastern Colombia. A total of 2,365 specimens and 10 species were captured using CDC light traps and Shannon traps, and from diurnal resting places, and human landing collections. Lutzomyia fairtigi Martins (55%), Lutzomyia micropyga (Mangabeira) (20.9%), and Lutzomyia antunesi (Coutinho) (13.5%) were the predominant species in the region. Lutzomyia flaviscutellata and Lutzomyia panamensis, potential vectors of Leishmania in Colombia and neighboring countries, were also collected, but in low numbers. Lu. fairtigi is an endemic species to Colombia, and minimal data are available on its biology and distribution. The present study provides additional information about Lu. fairtigi, such as the diurnal activity displayed by females on cloudy days, the greater density during the rainy season (April to October), marked anthropophilia, and the presence of flagellates in the midgut of one female.

It has been shown that the association of non-steroidal anti-inflammatory drugs (NSAIDs) with opioid analgesic agents can increase their antinociceptive activity, allowing the use of lower doses and thus limiting side effects. Therefore, the aim of the present study was to examine the possible pharmacological interaction between lumiracoxib and codeine or nalbuphine at the local peripheral level in the rat using the 1% formalin test and isobolographic analysis. Lumiracoxib, codeine, nalbuphine or fixed-dose ratios lumiracoxib-codeine or lumiracoxib-nalbuphine combinations were administrated locally in the formalin-injured paw and the antinociceptive effect was evaluated using the 1% formalin test. All treatments produced a dose-dependent antinociceptive effect. ED(40) values were estimated for the individual drugs and an isobologram was constructed. The derived theoretical ED(40)'s for the lumiracoxib-codeine and lumiracoxib-nalbuphine combinations were 423.4+/-31.3 microg/paw and 310.9+/-24.2 microg/paw, respectively, being significantly higher than the actually observed experimental ED(40) values, 233.2+/-30.9 microg/paw and 132.7+/-11.6 microg/paw, respectively. These results correspond to a synergistic interaction between lumiracoxib and opioids at the local peripheral level, potency being about two times higher with regard to that expected from the addition of the effects of the individual drugs. Data suggest that low doses of the lumiracoxib-opioids combination can interact synergistically at the peripheral level and therefore this drug association may represent a therapeutic advantage for the clinical treatment of inflammatory pain.

Persistent pulmonary hypertension of the newborn (PPHN) is a cardiopulmonary disorder characterized by systemic arterial hypoxemia secondary to elevated pulmonary vascular resistance with resultant shunting of pulmonary blood flow to the systemic circulation. PPHN is a serious illness that becomes progressively worse and is sometimes fatal. Management of the disease includes treatment of underlying causes, sedation and analgesia, maintenance of adequate systemic blood pressure, and ventilator and pharmacologic measures to increase pulmonary vasodilatation, decrease pulmonary vascular resistance, increase blood and tissue oxygenation, and normalize blood pH. Inhaled nitric oxide (NO) has been one of the latest measures to successfully treat PPHN. If all other treatments fail, extracorporeal membrane oxygenation (ECMO) can be used. Recently, preclinical and clinical studies have demonstrated the utility of the selective inhibitor of phosphodiesterase type 5 (PDE5), sildenafil, in decreasing pulmonary hypertension (HP). Sildenafil was first employed to offset rebound pulmonary hypertension in infants upon withdrawal of NO treatment. Later, several case reports demonstrated the effectiveness of sildenafil in the treatment of PPHN. Two randomized blinded studies with sildenafil in infants with PPHN were published in 2006. In both studies, the patients treated with sildenafil showed a steady improvement in pulse oxygen saturation over time. Likewise, the frequency death was lower in the groups treated with sildenafil. Recent evidence shows the utility of sildenafil in the treatment of PPHN. However, since existing data are limited there is an urgent need for multicenter blinded, placebo controlled, randomized trials.

The aim of this pilot study was to compare the efficacy and tolerability of the non-steroidal anti-inflammatory drug (NSAID), diclofenac (2-(2,6-dichloranilino) phenylacetic acid), for treatment of acute pain originated by lower-limb fracture and surgery, with that of diclofenac plus B vitamins. This clinical trial was single-center, prospective randomized and double-blinded. After giving informed consent, patients with lower-limb closed fractures rated their pain on a 10-cm visual analog scale (VAS). Patients were then randomized to receive 75 mg diclofenac or 75 mg diclofenac plus B vitamins (thiamine, pyridoxine and cyanocobalamin) twice daily (all intramuscularly). Patient evaluations of pain intensity were recorded throughout two periods: twenty-four hours pre-surgically and twenty-four hours postsurgical. Twenty-four hours after the first drug administration, patients underwent elective lower-limb surgery. Standardized general anesthetic techniques were used for all patients. Fourteen patients completed the study. The subjects' assessments of limb pain on the visual analog scale showed a significant reduction from baseline values regardless of the treatment group when surveyed at 12, 24, 36 and 48 hr post operation. All treatments showed a similar profile in pain reduction. There were reports of pain in the administration site, but in general, all the regimens were well tolerated.

Purpose: There are evidences that glibenclamide, a sulfonylurea antidiabetic agent, reduces the analgesic action of non-steroidal antiinflammatory drugs (NSAIDs), opioids and neuromodulators in animal models. The purpose of this work was to examine in the rat if such interaction involves pharmacokinetic mechanisms or is solely limited to the pharmacodynamic level., Methods: All studies were carried out in female Wistar rats. Analgesia was assessed using the formalin test. Fifty microliters of diluted formalin was injected subcutaneously into the dorsal surface of the right hind paw. Nociceptive behavior was quantified as the number of flinches of the injected paw during 60 min after injection and a reduction in formalin-induced flinching was interpreted as an analgesic response. Rats were treated with oral diclofenac (3-18 mg/kg) in presence and the absence of oral glibenclamide (1-30 mg/kg). To evaluate the possibility of a pharmacokinetic interaction, the oral bioavailability of diclofenac (18 mg/kg) was studied in presence and the absence of glibenclamide (10 mg/kg)., Results: Oral administration of diclofenac produced a dose-dependent antinociceptive effect in the formalin test. Coadministration of glibenclamide significantly reduced diclofenac-induced antinociception. Notwithstanding, the interaction does no appear to involve pharmacokinetic mechanisms, as oral glibenclamide failed to produce any significant alteration in oral diclofenac bioavailability., Conclusion: Concomitant systemic administration of glibenclamide and diclofenac results in a reduction of the analgesic effect of the NSAID in the formalin test in the rat. This interaction, however, appears due solely to a pharmacodynamic mechanisms as diclofenac pharmacokinetics are not altered.

It has been shown that the association of opioids analgesic agents with non-steroidal anti-inflammatory drugs (NSAIDs) can increase their antinociceptive activity, allowing the use of lower doses and thus limiting side effects. Therefore, the goal of the present study was to examine the possible pharmacological interaction between acemetacin and two opioids in the Hargreaves model of thermal hyperalgesia in the mouse. Acemetacin, codeine, nalbuphine or fixed-dose ratios acemetacin-codeine and acemetacin-nalbuphine combinations were administrated systemically to mice and the antihyperalgesic effect was evaluated using the thermal hyperalgesia test. All treatments produced a dose-dependent antihyperalgesic effect. ED40 values were estimated for all the treatments and an isobologram was constructed. The derived theoretical ED40 for the acemetacin-codeine and acemetacin-nalbuphine combinations were 55.9+/-4.9 mg/kg and 40.3+/-3.8 mg/kg, respectively, being significantly higher than the actually observed experimental ED40, 14.5+/-1.7 mg/kg and 12.7+/-2.2 mg/kg, respectively. These results correspond to synergistic interactions between acemetacin and opioids on the Hargreaves model of thermal hyperalgesia. Highest doses of the individual drugs or the combinations did not affect motor coordination in the balancing test on a rota-rod. Data suggest that low doses of the acemetacin-opioids combination can interact synergistically at systemic level and therefore this drugs association may represent a therapeutic advantage for the clinical treatment of inflammatory pain.

Allele frequencies for the 17 autosomic STRs loci including in the PowerPlex 16 System and Identifiler were estimated from unrelated individuals living in Buenos Aires province of Argentina.

Dysmenorrhea is defined as cramping pain in the lower abdomen occurring just before or during menstruation. Non-steroidal anti-inflammatory drugs (NSAIDs) are the mainstay of treatment, with the addition of oral contraceptive pills when necessary. With the widespread availability of over-the-counter NSAIDs, it is often assumed that women are treating themselves adequately. Unfortunately, this is not always the case. Therefore we evaluated the use of drugs for treating primary dysmenorrhea in Mexican students. A multiple-choice questionnaire was administered to 285 psychology students (20.6 +/- 2.4 yrs; range, 17-33 yrs), to assess the prevalence of dysmenorrhea and medications employed. The reported prevalence of dysmenorrhea among these women was 67%. Dysmenorrhea was mild in 34% moderate in 43% and severe in 21%. Of the dysmenorrheic sample, only 33.5% consulted physician in 2.6 +/- 0.2 cycles per year for their problem and the most common prescriptions were an over-the-counter medication with paracetamol pamabrom and pyrilamine maleate (Syncol; 22.4%) naproxen (18.4%), metamizole plus butylhyoscine bromide (10.2%), ibuprofen (6.1%) and butylhyoscine bromide (6.1%). On the other hand, self-medication was practiced by 64.9% of the women with dysmenorrhea in 6.1 +/- 3.8 cycles per year and the most common drugs by self-medication were Syncol (35.5%), naproxen (16.9%), metamizole plus naproxen butylhyoscine bromide (13.7%), an over-the-counter medication with adiphenine and propyphenazon (Espasmo-cibalgina; 10.5%), paracetamol (5.6%) butylhyoscine alone (4%) and ibuprofen (4%). Our data suggest that dysmenorrheic women use numerous drugs by self-medication for pain but infrequently accessed formal medical care.

There is evidence that local peripheral administration of codeine and morphine produces antinociception through the activation of the ATP-sensitive K(+)-channel. Therefore we evaluated the participation of this channel in the antinociceptive action produced by nalbuphine in the formalin test. Female Wistar rats (160-200 g) were injected in the dorsal surface of the right hind paw with 50 microl of formalin (5%). Nociception was quantified as the number of flinches of the injected paw during 1 hr, whereas a reduction of the number of flinches was considered antinociception. Rats received a s.c. injection (50 microl) into the dorsal surface of the right hind paw of vehicle or increasing doses of nalbuphine (100-400 microg/paw) 20 min before formalin injection into the ipsilateral paw. To determine whether nalbuphine-induced peripheral antinociception was mediated by K(+)-channels, the effect of pretreatment (10 min before formalin injection) with the appropriate vehicle or the ATP-sensitive K(+)-channel inhibitor glibenclamide (25-100 microg/paw) on the antinociceptive effect induced by local peripheral nalbuphine (400 microg/paw) was assessed. Morphine was used as positive antinociceptive control. Local peripheral injection of nalbuphine produced a dose-dependent antinociception during both phases of the test. Local pretreatment with glibenclamide prevented nalbuphine-induced antinociception in a dose-dependent fashion in both phases of the test. Our data suggest that nalbuphine activates ATP-sensitive K(+)-channels in order to produce its peripheral antinociceptive effect.

It has been shown that the association of diclofenac with other analgesic agents can increase its antinociceptive activity, allowing the use of lower doses and thus limiting side effects. Therefore, the aim of the present study was to examine the possible pharmacological interaction between diclofenac and gabapentin at the peripheral level in the rat using the 5% formalin test and isobolographic analysis. Diclofenac, gabapentin or a fixed-dose ratio diclofenac-gabapentin combination were administrated locally in the formalin-injured paw and the antinociceptive effect was evaluated using the 5% formalin test. All treatments produced a dose-dependent antinociceptive effect. ED30 values were estimated for the individual drugs and an isobologram was constructed. The derived theoretical ED30 for the diclofenac-gabapentin combination was 597.5+/-87.5 microg/paw, being significantly higher than the actually observed experimental value, 170.9+/-26.07 microg/paw. These results correspond to a synergistic interaction between diclofenac and gabapentin at the peripheral level, potency being about three times higher with regard to that expected from the addition of the effects of the individual drugs. Data suggest that low doses of the diclofenac-gabapentin combination can interact synergistically at the peripheral level and therefore this drug association may represent a therapeutic advantage for the clinical treatment of inflammatory pain.

The effect of modulators of the nitric oxide-cyclic GMP-protein kinase G-K+ channels pathway on the local peripheral antinociceptive action induced by gabapentin was assessed in the rat 1% formalin test. Local peripheral administration of gabapentin produced a dose-dependent antinociception in the second phase of the test. Gabapentin-induced antinociception was due to a local action as its administration in the contralateral paw was ineffective. Local peripheral pretreatment of the paws with NG-L-nitro-arginine methyl ester (L-NAME, a nitric oxide synthesis inhibitor), 1H-(1,2,4)-oxadiazolo(4,2-a)quinoxalin-1-one (ODQ, a soluble guanylyl cyclase inhibitor) and KT-5823 (a protein kinase G inhibitor) dose-dependently reduced gabapentin-induced antinociception. Likewise, glibenclamide or tolbutamide (ATP-sensitive K+ channel inhibitors), 4-aminopyridine or tetraethylammonium (non-selective inward rectifier K+ channel inhibitors) or charybdotoxin (large-conductance Ca2+-activated-K+ channel blocker), but not apamin (small-conductance Ca2+-activated-K+ channel blocker) or naloxone (opioid receptor antagonist), reduced the antinociception induced by gabapentin. Our data suggest that gabapentin could activate the nitric oxide-cyclic GMP-protein kinase G-K+ channels pathway in order to produce its peripheral antinociceptive effect in the rat 1% formalin test.

There is evidence that local peripheral administration of morphine produces antinociception through the activation of the nitric oxide (NO)-cyclic GMP-K(+) channels pathway. Therefore we evaluated the possible participation of this pathway in the antinociceptive action produced by codeine in the rat 5% formalin test. Local peripheral injection of codeine produced a dose-dependent antinociception during the first and second phases of the test. Local pretreatment of the paws with the NO synthase inhibitor N(G)-L-nitro-arginine methyl ester (L-NAME), the soluble guanylyl cyclase inhibitor methylene blue, the ATP-sensitive K(+) channel inhibitors glibenclamide and tolbutamide, the non-selective voltage-gated K(+) channel inhibitors 4-aminopyridine (4-AP) and tetraethylammonium (TEA) and the opioid receptor blocker naloxone prevented codeine-induced antinociception in both phases of the test. L-NAME, methylene blue, K(+) channel blockers and naloxone by themselves did not modify formalin-induced nociceptive behavior. Our data suggest that codeine could activate the opioid receptor-NO-cyclic GMP-K(+) channels pathway in order to produce its peripheral antinociceptive effect in the formalin test.

The possible participation of K+ channels in the antinociceptive action of meloxicam was assessed in the 1% formalin test. Local peripheral administration of meloxicam produced a dose-dependent antinociception only during the second phase of the formalin test. K+ channel blockers alone did not modify formalin-induced nociceptive behavior. However, local peripheral pretreatment of the paw with charybdotoxin and apamin (large- and small-conductance Ca2+-activated K+ channel inhibitors, respectively), 4-aminopyridine and tetraethylammonium (non-selective voltage-dependent K+ channel inhibitors), but not glibenclamide or tolbutamide (ATP-sensitive K+ channel inhibitors), dose-dependently prevented meloxicam-induced antinociception. It is concluded that meloxicam could open large- and small-conductance Ca2+-activated K+ channels, but not ATP-sensitive K+ channels, in order to produce its peripheral antinociceptive effect in the formalin test. The participation of voltage-dependent K+ channels was also suggested, but since non-selective inhibitors were used the data await further confirmation.

Evidence suggests that the ATP-sensitive K+ channels are important in the peripheral antinociceptive effect of diclofenac. Combinations of nonsteroidal anti-inflammatory drugs (NSAIDs) with other different drugs are currently used in clinical practice to increase the analgesic efficacy and to reduce adverse events. We evaluated the effect of the combination of diclofenac and the activator of K+ channels pinacidil in the formalin test. Female Wistar rats (180-200 g) were injected in the dorsal surface of the right hind paw with 50 microl of formalin (1%). Nociception was quantified as the number of flinches of the injected paw during the next 60 mins, while reduction of flinches was considered antinociception. Ipsilateral, but not contralateral, pretreatment with diclofenac (25-200 microg/paw) or pinacidil (5-50 microg/paw) significantly reduced, in a dose-dependent manner the formalin-induced flinching behavior during the second phase of the test. To determine if pinacidil was able to increase the effect of diclofenac, noneffective increasing doses of pinacidil were coadministered with an ineffective dose of diclofenac (25 microg). The local co-administration of pinacidil and diclofenac produced a significant reduction in the number of flinches during phase 2, but not during phase 1 of the test compared to the effect of either drug alone. In conclusion, the combination of individually ineffective doses of diclofenac and pinacidil produce an antinociceptive effect in the formalin test. In addition, pinacidil increased the action of diclofenac, probably through the activation of K+ channels.

Background: The impact of obesity on survival in end-stage renal disease (ESRD) patients as related to dialysis modality (i.e., a direct comparison of hemodialysis with peritoneal dialysis) has not been assessed adjusting for differences in medication use, follow-up > or =2 years, or accounting for changes in dialysis modality., Methods: We performed a retrospective cohort study of the United States Renal Data System (USRDS) Dialysis Morbidity and Mortality Wave II Study (DMMS) patients who started dialysis in 1996, and were followed until October 31 2001. Cox regression analysis was used to model adjusted hazard ratios (AHR) for mortality for categories of body mass index (BMI), both as quartiles and as > or =30 kg/m2 vs. lower. Because such a large proportion of peritoneal dialysis patients changed to hemodialysis during the study period (45.5%), a sensitivity analysis was performed calculating survival time both censoring and not censoring on the date of change from peritoneal dialysis to hemodialysis., Results: There were 1675 hemodialysis and 1662 peritoneal dialysis patients. Among hemodialysis patients, 5-year survival for patients with BMI > or =30 kg/m2 was 39.8% vs. 32.3% for lower BMI (P < 0.01 by log-rank test). Among peritoneal dialysis patients, 5-year survival for patients with BMI >/=30 kg/m2 was 38.7% vs. 40.4% for lower BMI (P > 0.05 by log-rank test). In adjusted analysis, BMI > or = 30 kg/m2 was associated with improved survival in hemodialysis patients (AHR 0.89; 95% CI 0.81, 0.99; P= 0.042) but not peritoneal dialysis patients (AHR = 0.99; 95% CI, 0.86, 1.15; P= 0.89). Results were not different on censoring of change from peritoneal dialysis to hemodialysis., Conclusion: We conclude that any survival advantage associated with obesity among chronic dialysis patients is significantly less likely for peritoneal dialysis patients, compared to hemodialysis patients.

The distribution of the vertebrate telomeric sequence T2AG3 in three species of the rodent genus Akodon was examined by FISH with a peptide nucleic acid probe. In addition to the expected telomeric hybridization, non-telomeric signals were observed in the three species. In A. dolores, centromeric signals were visible in two of the four biarmed autosome pairs featuring Robertsonian polymorphism, indicating the retention of at least part of the telomeric sequences during the fusion process, and an interstitial signal of lower intensity was observed in the short arm of another. In A. boliviensis, a strong signal was observed near the centromeric end of the first chromosome pair. The first pair of A. azarae (homologous to the first pair of A. boliviensis) showed a similar but markedly amplified signal, and a subcentromeric signal in the X chromosome corresponding to a heterochromatic region; additionally, interstitial signals of lower intensity were present in one to four chromosomes in the majority of cells examined., (Copyright 2004 S. Karger AG, Basel)

This study was designed to evaluate the extent of the antinociceptive interaction between codeine and diclofenac at the local, spinal and systemic level. The effects of individual and fixed-ratio combinations of locally, spinally or orally given codeine and diclofenac were assayed using the formalin test in rats. Isobolographic analysis was employed to characterize the synergism produced by the combinations. Codeine, diclofenac and fixed-ratio codeine-diclofenac combinations produced a dose-dependent antinociceptive effect when administered locally, spinally or systemically. ED(30) values were estimated for the individual drugs and isobolograms were constructed. Theoretical ED(30) values for the combination estimated from the isobolograms were 422.2+/-50.5 microg/paw, 138.5+/-9.2 microg/rat, and 9.3+/-1.1 mg/kg for the local, spinal and oral routes, respectively. These values were significantly higher than the actually observed ED(30) values which were 211.1+/-13.6 microg/paw, 45.9+/-3.9 microg/rat, and 2.5+/-0.2 mg/kg, indicating a synergistic interaction. Systemic administration resulted in the highest increase in potency, being about fourfold, while spinal and local administration increased potency in two- and threefold, respectively. The fact that the highest synergism was observed after systemic administration suggests that the interaction is occurring at several anatomical sites. The results support the clinical use of this combination in pain management.

The aim of this study was to examine if the peripheral antinociceptive effects of diclofenac and indomethacin involve the sequential participation of NO and cGMP synthesis followed by potassium channel opening. The peripheral antinociceptive effects of diclofenac, indomethacin, pinacidil (a potassium channel opener) and atrial natriuretic peptide (ANP, which increases cGMP content in a NO-independent manner) were assayed using the formalin test in the rat. All compounds produced significant local antinociception. Diclofenac effect was reverted by N(G)-L-nitro-arginine methyl ester (L-NAME, an inhibitor of NO synthesis), by 1 H-(1,2,4)-oxadiazolo (4,2-a) quinoxalin-1-one (ODQ, an inhibitor soluble guanylyl cyclase), and by the potassium channel blockers glibenclamide, tolbutamide, charybdotoxin and apamin. Pinacidil effect was blocked by glibenclamide, tolbutamide, charybdotoxin and apamin, strongly suggesting that potassium channel opening results in antinociception. ANP effect was inhibited by the potassium channel blockers, but not by L-NAME, suggesting that potassium channel opening is a consequence of an increased cGMP content. Indomethacin was effective, but at doses higher than those of diclofenac, and could not be blocked by L-NAME nor by potassium channel blockers. The present results suggest that the L-arginine-NO-cGMP-potassium channel pathway is involved in the peripheral antinociceptive effect of diclofenac, but not of indomethacin, and thus provide evidence for differences in mechanisms of action among nonsteroidal antiinflammatory drugs (NSAIDs).

The present work assessed the possible participation of K+ channels in the peripheral antinociceptive action of metamizol in the 1% formalin test. Ipsilateral, but not contralateral, local peripheral administration of metamizol produced a dose-dependent antinociception only during the second phase of the formalin test. K+ channel blockers alone did not modify formalin-induced nociceptive behavior. However, local peripheral pretreatment of the paw with charybdotoxin and apamin (large- and small-conductance Ca(2+)-activated K+ channel blockers, respectively), 4-aminopyridine and tetraethylammonium (voltage-dependent K+ channel inhibitors), but not glibenclamide or tolbutamide (ATP-sensitive K+ channel inhibitors), dose-dependently prevented metamizol-induced antinociception. The above results suggest that metamizol could open large- and small-conductance Ca(2+)-activated K+ channels, but not ATP-sensitive K+ channels, in order to produce its peripheral antinociceptive effect in the formalin test. The participation of voltage-dependent K+ channels was also suggested, but since nonselective inhibitors were used, the data await further confirmation.

The possible participation of K(+) channels in the antinociceptive action induced by resveratrol was assessed in the 1% formalin test. Local administration of resveratrol produced a dose-dependent antinociception in the second phase of the test. The antinociception produced by resveratrol was due to a local action as its administration in the contralateral paw was not active. Local pretreatment of the injured paw with glibenclamide, tolbutamide or glipizide (ATP-sensitive K(+) channel inhibitors) did not modify resveratrol-induced antinociception. In contrast, charybdotoxin and apamin (large and small conductance Ca(2+) activated-K(+) channel blockers, respectively), 4-aminopyridine or tetraethylammonium (voltage-dependent K(+) channel inhibitors) dose-dependently prevented resveratrol-induced antinociception. Local peripheral administration of glibenclamide, but not charybdotoxin or apamin, significantly reduced the antinociceptive effect produced by peripheral morphine (positive control). At the highest effective doses, none of the drugs used induced behavioral side effects as revealed by the evaluation of stepping, righting, corneal and pinna reflexes. In addition, when given alone, none of the inhibitors modified the nociceptive behavior induced by 1% formalin. The results suggest that resveratrol opens large and small conductance Ca(2+)-activated K(+) channels, but not ATP-sensitive K(+) channels, in order to produce its peripheral antinociceptive effect in the formalin test. The participation of voltage-dependent K(+) channels was also suggested, but since non-selective inhibitors were used the data awaits further confirmation.

1. In pithed rats, 5-HT mediates tachycardia both directly (by 5-HT(2) receptors) and indirectly (by a tyramine-like effect). The receptor mediating tachycardia directly has been classified as an 'atypical' 5-HT(2) receptor since it was 'weakly' blocked by ketanserin. Moreover, 1-(2,5-dimethoxy-4-iodophenyl)-2-aminopropane (DOI), a 5-HT(2) agonist, failed to mimic 5-HT-induced tachycardia. Since 5-HT(2) receptors consist of 5-HT(2A), 5-HT(2B) and 5-HT(2C) subtypes, this study investigated if these subtypes mediate the above response. 2. In pithed rats, intraperitoneally (i.p.) pre-treated with reserpine (5 mg kg(-1)), intravenous (i.v.) administration of 5-HT, 5-methoxytryptamine (5-MeO-T), 1-(3-chlorophenyl) piperazine (mCPP) and 5-carboxamidotryptamine (5-CT) (10, 30, 100 and 300 microg kg(-1) each), produced dose-dependent tachycardic responses. Interestingly, DOI (10 - 1000 microg kg(-1), i.v.) induced only slight, dose-unrelated, tachycardic responses, whilst the 5-HT(2C) agonist, Ro 60-0175 (10 - 1000 microg kg(-1), i.v.), produced a slight tachycardia only at 300 and 1000 microg kg(-1). In contrast, sumatriptan and 1-(m-trifluoromethylphenyl)- piperazine (TFMPP) were inactive. The rank order of potency was: 5-HT > or =5-MeO-T> mCPP > or =5-CT > or =DOI > Ro 60-0175. 3. The tachycardic responses to 5-HT, which remained unaffected after i.v. saline (0.3 and 1 ml kg(-1)) or propranolol (3 mg kg(-1)), were selectively blocked by the 5-HT(2A) antagonists ketanserin (30 and 100 microg kg(-1)) or spiperone (10 and 30 microg kg(-1)) as well as by the non-selective 5-HT(2) antagonists, ritanserin (10 and 30 microg kg(-1)) or mesulergine (100 microg kg(-1)). Remarkably, these responses were unaffected by the antagonists rauwolscine (5-HT(2B)), SB204741 (5-HT(2B/2C)) or Ro 04-6790 (5-ht(6)) (300 and 1000 microg kg(-1) each). 4. These results suggest that the 'atypical' 5-HT(2) receptors mediating tachycardia in reserpinized pithed rats are pharmacologically similar to the 5-HT(2A) receptor subtype.

The involvement of K(+) channels in the antinociceptive action of diclofenac was assessed in the formalin test. Local administration of diclofenac produced a dose-dependent antinociceptive effect due to a local action because drug administration in the contralateral paw was ineffective. Pretreatment of the injured paw with glibenclamide and tolbutamide (ATP-sensitive K(+) channel inhibitors), charybdotoxin and apamin (large- and small-conductance Ca(2+)-activated K(+) channel blockers, respectively), 4-aminopyridine or tetraethylammonium (voltage-dependent K(+) channel inhibitors) prevented diclofenac-induced antinociception. Given alone, K(+) channel inhibitors did not modify formalin-induced nociceptive behavior. Pinacidil (an ATP-sensitive K(+) channel opener) also produced antinociception which was blocked by glibenclamide. The peripheral antinociceptive effect of morphine (positive control) was blocked by glibenclamide and 4-aminopyridine but not by charybdotoxin or apamin. The results suggest that the peripheral antinociceptive effect of diclofenac may result from the activation of several types of K(+) channels, which may cause hyperpolarization of peripheral terminals of primary afferents.

The peripheral antinociceptive effect of the selective COX-2 inhibitor celecoxib in the formalin-induced inflammatory pain was compared with that of resveratrol (COX-1 inhibitor) and diclofenac (non-selective COX inhibitor). Rats received local pretreatment with saline, celecoxib, diclofenac or resveratrol followed by 50 microl of either 1% or 5% formalin. Peripheral administration of celecoxib did not produce antinociception at either formalin concentration. In contrast, diclofenac and resveratrol produced a dose-dependent antinociceptive effect in the second phase of both 1% and 5% formalin test. The peripheral antinociception produced by diclofenac or resveratrol was due to a local action, as drug administration in the contralateral paw was ineffective. Results indicate that the selective COX-2 inhibitor celecoxib does not produce peripheral antinociception in formalin-induced inflammatory pain. In contrast, selective COX-1 and non-selective COX inhibitors (resveratrol and diclofenac, respectively) are effective drugs in this model of pain.

The present study has investigated the preliminary pharmacological profile of the receptors mediating vasoconstriction to 5-hydroxytryptamine (5-HT) in the internal carotid bed of vagosympathectomised dogs. One minute intracarotid infusions of the agonists 5-HT (0.1 - 10 microg min(-1)), sumatriptan (0.3 - 10 microg min(-1); 5-HT(1B/1D)), 5-methoxytryptamine (1 - 100 microg min(-1); 5-HT(1), 5-HT(2), 5-HT(4), 5-ht(6) and 5-HT(7)) or DOI (0.31 - 10 microg min(-1); 5-HT(2)), but not 5-carboxamidotryptamine (0.01 - 0.3 microg min(-1); 5-HT(1), 5-ht(5A) and 5-HT(7)), 1-(m-chlorophenyl)-biguanide (mCPBG; 1 - 1000 microg min(-1); 5-HT(3)) or cisapride (1 - 1000 microg min(-1); 5-HT(4)), resulted in dose-dependent decreases in internal carotid blood flow, without changing blood pressure or heart rate. The vasoconstrictor responses to 5-HT, which remained unaffected after saline, were resistant to blockade by i.v. administration of the antagonists ritanserin (100 microg kg(-1); 5-HT(2A/2B/2C)) in combination with tropisetron (3000 microg kg(-1); 5-HT(3/4)) or the cyclo-oxygenase inhibitor, indomethacin (5000 microg kg(-1)), but were abolished by the 5-HT(1B/1D) receptor antagonist, GR127935 (30 microg kg(-1)). Interestingly, after administration of GR127935, the subsequent administration of ritanserin unmasked a dose-dependent vasodilator component. GR127935 or saline did not practically modify the vasoconstrictor effects of 5-MeO-T. In animals receiving GR127935, the subsequent administration of ritanserin abolished the vasoconstrictor responses to 5-MeO-T unmasking a dose-dependent vasodilator component. The vasoconstriction induced by sumatriptan was antagonized by GR127935, but not by ritanserin. Furthermore, ritanserin (100 microg kg(-1)) or ketanserin (100 microg kg(-1); 5-HT(2A)), but not GR127935, abolished DOI-induced vasoconstrictor responses. The above results suggest that 5-HT-induced internal carotid vasoconstriction is predominantly mediated by 5-HT(1B/1D) and 5-HT(2A) receptors.

The vasoconstrictor effects of 5-hydroxytryptamine (5-HT) in the internal carotid bed of anaesthetised dogs with bilateral vagosympathectomy are mainly mediated by both 5-HT1B and 5-HT2 receptors. The blockade of this vasoconstrictor effect of 5-HT by the combined use of the antagonists, GR127935 (5-HT1B/1D) and ritanserin (5-HT2), unmasks a dose-dependent vasodilator effect of 5-HT, but not of sumatriptan. Therefore, the present study set out to analyse the pharmacological profile of this vasodilator 5-HT receptor in the internal carotid bed of vagosympathectomized dogs systematically pretreated with intravenous (i.v.) injections of GR127935 (30 microg/kg) and ritanserin (100 microg/kg). One-minute (1-min) intracarotid (i.c.) infusions of 5-HT (0.1-10 microg/min), 5-carboxamidotryptamine (5-CT; 0.01-0.3 microg/min), 5-methoxytryptamine (5-MeO-T; 1-100 microg/min) and acetylcholine (ACh; 0.003-0.1 microg/min) resulted in dose-dependent increases in internal carotid blood flow (without changes in blood pressure or heart rate) with a rank order of agonist potency of ACh > 5-CT >> 5-HT > or =5-MeO-T. The internal carotid vasodilator responses to 5-HT, 5-CT and 5-MeO-T, which remained unaffected after saline (0.03 ml/kg and 0.1 ml/kg, i.v.), were specifically and dose-dependently blocked by i.v. administration of lisuride (10 microg/kg and 30 microg/kg), clozapine (1000 microg/kg), mesulergine (300 microg/kg and 1000 microg/kg) and LY215840 (300 microg/kg and 1000 microg/kg) with the following apparent rank order of potency: lisuride >> mesulergine = LY215840 > or = clozapine. The above results suggest that the 5-HT receptor mediating internal carotid vasodilatation in vagosympathectomized dogs pretreated with GR127935 and ritanserin is operationally similar to other 5-HT7 receptors mediating vascular and non-vascular responses.

It has been suggested that the late hypotensive response to serotonin (5-hydroxytryptamine; 5-HT) in vagosympathectomised cats, being potently mimicked by 5-carboxamidotryptamine (5-CT), not modified by ketanserin and blocked by methiothepin or methysergide, is mediated by '5-HT1-like' receptors. Nevertheless, current guidelines for 5-HT receptor classification refer to this receptor as an orphan receptor. Thus, the present study set out to reanalyse the above suggestion in terms of the classification schemes proposed in 1994 and 1998 by the NC-IUPHAR subcommittee on the classification of 5-HT receptors. Intravenous (i.v.) bolus injections of 5-CT (0.003-0.3 microg/kg), 5-HT (1-100 microg/kg) and 5-methoxytryptamine (5-MeO-T; 1-100 microg/kg) produced dose-dependent vasodepressor responses with a rank order of agonist potency of 5-CT >> 5-HT = 5-MeO-T with sumatriptan (10-300 microg/kg) virtually inactive. The vasodepressor responses to 5-HT, 5-CT and 5-MeO-T were not attenuated following i.v. administration of the antagonists GR127935 (5-HT(IB/ID); 30 microg/kg), tropisetron (5-HT3/4; 3000 microg/kg), (+/-)-pindolol (beta-adrenergic and 5-HT1A; 4000 microg/kg) or equivalent volumes of physiological saline. In contrast, the above vasodepressor responses were markedly and specifically antagonised by i.v. methiothepin (100 microg/kg), lisuride (30 microg/kg and 100 microg/kg), mesulergine (300 microg/kg and 1000 microg/kg) or LY215840 (300 microg/kg and 1000 microg/kg). The above lines of evidence, therefore, indicate that the orphan receptors mediating the vasodepressor responses to 5-HT in vagosympathectomised cats are pharmacologically similar to other 5-HT7 receptors mediating vascular and non-vascular responses (e.g. relaxation of the canine external carotid artery and guinea-pig ileum as well as feline tachycardia).

The bis-benzimidazole compound nuclear yellow (NY) belongs to the same chemical family as the DNA binding fluorochromes Hoechst 33258 and Hoechst 33342. Spectroscopic studies of NY alone and in the presence of calf thymus DNA show high DNA binding affinity and behavior similar to the Hoechst fluorochromes above. Mitotic metaphase chromosomes from Balb/c mice stained with NY show C-banding and weak G/Q-banding, both of them disappearing after distamycin A (DA) or methyl green (MG) counterstaining. The same staining of human metaphase chromosomes from lymphocyte cultures, however, reveal only faint G/Q-banding (NY) and a characteristic DA-DAPI-like banding (NY-DA, NY-MG). Image analysis of NY stained human chromosomes, confirms that NY is suitable for studying polymorphisms affecting size in the pericentromeric heterochromatin of pairs 1, 9 and 16, and shows significant enhancement of NY fluorescence induced by DA in DA-DAPI heterochromatin. Our spectroscopic and cytological results show that NY, either alone or counterstained with DA or MG, can be used for DNA cytochemistry and chromosome banding. Possible mechanisms for the banding patterns induced by NY are discussed.

The EcoEléctrica Mangrove Planting Project, a five-year voluntary effort, has the purpose of testing a recently developed mangrove planting technique at the EcoEléctrica site in Peñuelas, Puerto Rico. The goal of the project is to provide empirical validation to promote or improve the technique to be used in recovering mangrove ecosystems in Puerto Rico and United States. The research presented herein analyzed the information collected on the first two years of the project. The proportions of remaining casings and seeds per study zone were compared using the chi-square distribution. Zone 1 had the least pipes lost while Zone 4 had the most (p < 0.05). Forty-three percent of the seeds in Zone 1 remained in the casing, while 26% remained in Zone 2 (p = 0.03). Median growth rates of seeds per study zone showed that Zone 1 had the highest median growth rates. Survival analysis described the survival experience of the seeds, and differences in survival probabilities were compared with the log-rank test. Zone 1 seeds had a better survival experience compared to Zones 2, 3 and 4 (p < 0.0001). Survival probabilities for being free of spots were over 60% during the whole study period. No significant differences were observed in the survival experience with the use-or-no use of casing extensions (p = 0.40), and the use-or-no use of nursed seeds (p = 0.26). Differences in survival probabilities might be attributed to variations in wave energy, depth or substrate conditions. This hypothesis will be evaluated in the second phase of the study.