N alpha methyl histamine versus propranolol in migraine prophylaxis.

OBJECTIVES: To compare the efficacy and tolerability of the subcutaneous administration of N alpha methyl histamine versus oral propranolol in the treatment of migraine prophylaxis. BACKGROUND: N alpha methyl histamine has a selective affinity for H3 receptors and could constitute a new therapeutic drug in migraine prophylaxis. METHODS: Sixty patients with migraine were selected and enrolled in a 12-week double-blind controlled clinical trial to evaluate the efficacy of subcutaneous administration of N-alpha methyl histamine (1 to 3 ug twice a week ) n=30, compared to administration of 120 mg/day of oral propranolol n=30. the variables were: headache intensity, frequency of attacks, duration of migraine attacks and analgesic intake. RESULTS: fifty five patients completed the study. the data collected during the 4th week of treatment revealed that N alpha methyl histamine and propranolol caused a significantly (p<0.01) greater reduction between the basal values and final values of every variable studied. CONCLUSIONS: Both N alpha methyl histamine and propranolol are similarly effective in reducing or eliminating the headache in migraine prophylaxis. low doses of N-alpha methyl histamine injected subcutaneously may represent a novel and effective therapeutic alternative in migraine patients and may lay the clinical and pharmacological groundwork for the use of H3 receptor agonist in migraine prophylaxis.

Prevalence of childhood sexual abuse among Mexican adolescents.

BACKGROUND: To determine the characteristics and prevalence of previous child sexual abuse among a group of Mexican junior high school students. METHODS: A total of 1067 adolescents of both genders were selected to fill out a survey about child sexual abuse. RESULTS: The prevalence of child sexual abuse was 18.7% (n = 200). It was more frequent in girls (58%) than in boys (42%). Sexual abuse involved physical contact in 75% of those cases reporting abuse. The aggressors were neighbours (50.3%), relatives (36.8%) and strangers (13.9%). Abuse was committed through deception in 90% of the cases and involved physical mistreatment in 10% of the cases. Of the victims, 14.4% had spoken about the problem and 3.7% had taken legal action. And 9.6% of those surveyed stated that they required psychological counselling. CONCLUSIONS: In the population studied, the prevalency of child sexual abuse was greater than that reported in Mexico City (4.3-8.4%), although it was similar to that found in the Spanish child population (15-23%). The risk of sexual abuse is greater for girls and the principal aggressors are male neighbours, family friends and relatives; the abuse is committed in the home of the aggressor or the victim and very few cases are reported to the authorities.

Subcutaneous histamine versus botulinum toxin type A in migraine prophylaxis: a randomized, double-blind study.

OBJECTIVES: To compare the efficacy and tolerability of the subcutaneous administration of histamine and botulinum toxin type A (BoNTA) in migraine prophylaxis. BACKGROUND: Histamine has a selective affinity for H3 receptors and it may specifically inhibit the neurogenic edema response involved in migraine pathophysiology. METHODS: One hundred patients with migraine were selected in a 12-week double-blind controlled clinical trial to evaluate the efficacy of subcutaneous administration of histamine (1-10 ng twice a week) n = 50, compared with administration of 50 U of BoNTA (one injection cycle) n = 50. RESULTS: The data collected during the 4th week of treatment revealed a significant decrease in all parameters studied, in histamine and BoNTA (P < 0.001). After 4 weeks of treatment, but one injection cycle of 50 U BoNTA had only a 40-day period of efficacy. CONCLUSIONS: This randomized study demonstrated that both histamine and BoNTA are similarly effective and well tolerated in reducing or eliminating headache in migraine prophylaxis. Low doses of histamine applied subcutaneously may represent a novel and effective therapeutic alternative in migraine patients and lay the clinical and pharmacological groundwork for the use of H3 agonist in migraine prophylaxis.

Reduction of peritoneal adhesion to polypropylene mesh with the application of fibrin glue.

PURPOSE: The purpose of our study was to evaluate the possibility of the reduction of peritoneal adhesions to a polypropylene mesh with fibrin glue. METHODS: Forty Wistar rats were assigned to two treatment groups: Group 1) hernioplasty with polypropylene mesh plus fibrin glue sealant, and Group 2) hernioplasty with polypropylene mesh without fibrin glue sealant. The variables evaluated were: presence and density of adhesion, organs or abdominal structures adhered to the polypropylene mesh, inflammatory tissular reaction and cell recount. RESULTS: Group 1 presented a statistically lower adhesion percentage than Group 2 (40% versus 100%, P = 0.0003). The mean areas of mesh patch surfaces covered with adhesions were statistically different between Groups 1 and 2 (0.67 +/- 0.65 cm2 versus 1.60 +/- 0.51 cm2; P = 0.00001). Twelve rats presented with adhesions in Group 1; eleven were adhesions to the epiploon and one to the colon. In Group 2 there were 16 adhesions to the epiploon, 2 to the colon, 1 to the small intestine and 1 to the stomach. Tissular reaction comparison showed a significant difference (21 +/- 4.9 versus 17 +/- 4.1; P = 0.006). CONCLUSIONS: Fibrin glue sealant significantly reduced the frequency and severity of intra-abdominal adhesions.

Subcutaneous histamine versus topiramate in migraine prophylaxis: a double-blind study.

BACKGROUND: Histamine has a selective affinity for H3 receptors and it may specifically inhibit the neurogenic edema response involved in migraine pathophysiology. OBJECTIVE: To evaluate the therapeutic potential of subcutaneous administration of histamine in migraine prophylaxis, compared with oral administration of topiramate. METHODS: Ninety patients with migraine were selected in a 12-week double-blind controlled clinical trial to evaluate the efficacy of subcutaneous administration of histamine (1-10 ng twice a week) compared with oral administration of topiramate (100 mg daily dose). The variables studied were: headache intensity, frequency, duration, analgesic intake and Migraine Disability Assessment. RESULTS: The data collected during the 12 weeks of treatment revealed that headache symptoms improved in both the histamine and topiramate groups, which was evident within the first month after the initiation of treatment, with statistically significant (p < 0.001) reductions in headache frequency (50%), Migraine Disability Assessment score (75%), intensity of pain (51%), duration of migraine attacks (45%), as well as in the use of rescue medication (52%). CONCLUSION: The present study provides evidence of the efficacy of subcutaneously applied histamine and orally administered topiramate in migraine prophylaxis. Subcutaneously applied histamine may represent a novel and effective therapeutic alternative in resistant migraine patients.

Subcutaneous histamine versus sodium valproate in migraine prophylaxis: a randomized, controlled, double-blind study.

Histamine has a selective affinity for H3-receptors and it may specifically inhibit the neurogenic edema response involved in migraine pathophysiology. The objective of this study was to evaluate the therapeutic potential of subcutaneous administration of histamine in migraine prophylaxis, compared with oral administration of sodium valproate, in an open clinical trial. Ninety-two patients with migraine were selected under criteria established by the International Headache Society and enrolled in a 12-week double-blind controlled clinical trial to evaluate the efficacy of subcutaneous administration of histamine (1-10 ng twice a week; n = 46) compared with oral administration of sodium valproate (500 mg daily dose; n = 46). The variables studied were headache intensity, frequency, duration, analgesic intake and migraine disability assessment (MIDAS). Two-tailed Student's t- test was used to compare means and the Mann-Whitney U and anova tests were used. The data collected during the 4th, 8th and 12th weeks of treatment revealed that histamine caused a significantly greater reduction (P < 0.001) in intensity and duration of migraine attacks as well as in analgesic intake. No difference was detected in the frequency of attacks or in MIDAS. The present study provides evidence of the superior efficacy of histamine applied subcutaneously in migraine prophylaxis when compared with sodium valproate taken orally. Subcutaneously applied histamine may represent a novel and effective therapeutic alternative in resistant migraine patients.

Preliminary studies of Mammea americana L. (Guttiferae) bark/latex extract point to an effective antiulcer effect on gastric ulcer models in mice.

Plant extracts are some of the most attractive sources of new drugs and have shown promising results for the treatment of gastric ulcers. Several folk medicinal plants and herbs have been used to treat gastrointestinal disorders, including gastric ulcers. Mammea americana L. (Guttiferae) fruit is very common in the diet of the population of northern South America. Our research interest in this plant arose because of its potential medicinal value as a tonic and against stomachache, as used in folk medicine. In this paper we evaluated three different extracts (ethanolic/EtOH, methanolic/MeOH and dichloromethane/DCM) obtained from M. americana L., for their ability to protect the gastric mucosa against injuries caused by necrotizing agents (0.3 M HCl/60% EtOH), hypothermic restraint stress, nonsteroidal anti-inflammatory drugs (NSAID, indomethacin) and pylorus ligation. In the HCl/EtOH-induced gastric-ulcer model, EtOH and DCM extracts demonstrated significant inhibition of the ulcerative lesion index by 54% (12.0 +/- 2.6 mm) and 86% (3.7 +/- 1.8 mm), respectively, in relation to the control value (26.0 +/- 1.4 mm) (p<0.0001). In the NSAID/cholinomimetic-induced lesion model, both EtOH and DCM extracts showed antiulcerogenic effects with significant reduction in the damage to these gastric lesions of 36% (8.3 +/- 2.0 mm) and 42% (7.5 +/- 1.4 mm), respectively, as compared to the control group (13.0 +/- 0.9 mm) (p<0.0001). In the gastric ulcer induced by hypothermic-restraint stress, both extracts also showed significant activity, and inhibited the gastric lesion index by 58% and 75%, respectively. The EtOH and DCM extracts also changed gastric juice parameters as well as those of cimetidine, decreased gastric acid secretion significantly (p<0.0001), increased pH values and promoted reduced acid output (p<0.0001). In all gastric-ulcer-induced models, MeOH extract did not show any significant antiulcerogenic activity, nor did it change gastric-juice parameters (p>0.05). The results suggest that EtOH and DCM extracts obtained from M. americana possess excellent antisecretory and/or gastrotective effect in all gastric ulcer models. These results suggest that the antiulcerogenic compound(s) present in M. americana may be clustered in the apolar fraction, which will be investigated by our group for the probable mechanisms of action.

Correlation between serum leptin levels and insulin sensitivity in diffuse toxic goiter.

OBJECTIVE: The aim of this survey was to assess the correlation between leptin and insulin sensitivity (IS) in cases of diffuse toxic goiter. DESIGN, PATIENTS, MEASUREMENTS: This is a descriptive study on patients with diffuse toxic goiter (DTG) assessing their body mass index (BMI), serum leptin concentrations, circulating insulin (area under the curve (AuC) of insulin), average insulin level, thyroid hormones, thyroid stimulating hormone (TSH), glycemia and IS (using a hyperinsulinemic-euglycemic clamp and the homeostasis model for assessment of insulin resistance (HOMA-IR) before and after euthyroidism induced with metimazol. RESULTS: The average patient age was 35 years old (range 31-40 years), height was 157 cm (range 151-160 cm), glycemia was 4.3 +/- 0.3 mmol/L and TSH 0.1 +/- 0.1 microU/mL. Average leptin level was 11.3 +/- 2.8 ng/dL, the average insulin level was 10.13 +/- 3.7 mIU/mL and the AuC for insulin was 50.6 +/- 18 microIU x min/mL. No correlation was found between leptin and BMI, thyroid hormones and glycemia. While controlling for the BMI effect, a correlation was found between leptin and TSH (r = -0.77, p = 0.042), as well as between leptin and insulinemia (r = 0.93, r2 = 0.86, p = 0.001) independently from the state of thyroid function. There was a tendency for a high correlation between leptin and the insulin AuC (hyperthyroidism: r = 0.89, p = 0.056; euthyroidism: r = 0.99, p = 0.056). A negative correlation was found between IS and the insulin AuC (rho = -0.58, p = 0.18). There was a high tendency for correlation between leptin and IS when the BMI effect (HOMA-IR: r = 0.70, p = 0.12; PHE: r = -0.55, p = 0.26) was taken into consideration. CONCLUSIONS: There is a high tendency for a negative correlation between leptin and IS when the BMI effect is controlled. There is a high tendency for a positive correlation between leptin and insulin and TSH.

Bioassay screening of Amazonian plants

OBJECTIVE: The purpose of this study was to evaluate several biological activities of thirty plant extracts collected in the North West Amazon (Ecuador). Some of these plants are being used for their reputed medicinal properties by the natives of this region. METHODS: Five in vitro bioassays were used to screen the plant material. 1. The brine shrimp lethality examination (BSLT) in microplate is a general test that seems capable of detecting a broad spectrum of bioactivity present in crude plant extracts. 2. Free radical scavenging properties were studied in a colorimetric assay using 2,2-diphenyl-1-picrylhydrazyl (DPPH). 3. The beta-glucosidase inhibition test is thought to be a method for the evaluation of anti-AIDS, anti-diabetic or anti-obesity compounds. 4. The xanthine oxidase inhibition assay is used to identify potential anti-gout agents. 5. The antibacterial activity that is being used to isolate and identify antibiotic drugs. RESULTS: In the BSLT, we found that Piscidia carthagenensis demonstrated very good activity with a LC50: 21.81 micrograms/mL. It is considered that plant extracts with low LC50 values may contain metabolites with cytotoxic, antifungal, insecticidal or pesticide activities. In the antioxidant activity bioassay, several plant extracts were confirmed to have excellent free radical scavenging properties. Rhus juglandifolia and Clusia venusta leaves exhibited an ED50: 3.12 micrograms/mL and 3.61 micrograms/mL, respectively. Piper reticulatum (84 per cent), Inga heteroptera (77 per cent), Clusia venusta (70.9 per cent), and Rhus juglandifolia (70.5 per cent) showed fairly good inhibition activity for beta-glucosidase. On the other hand, none of the plant extracts was capable of inhibiting xanthine oxidase. Finally, the Gram-positive microorganisms Staphylococcus aureus and Corynebacterium diphteriae were found to be sensitive to the majority of the plant extracts, whereas the Gram-negative bacteria Escherichia coli, Pseudomonas aeruginosa, Proteus vulgaris, and Salmonella typhi were proved to be resistant toward the plant extracts. CONCLUSIONS: It is important to continue investigating our plant kingdom, especially the world tropical reserves as an alternative for finding new or better drugs. It should be essential to follow-up this type of investigation to isolate and elucidate the active principles of the bio-positive plants.

[Levodopa in hemifacial spasm. A therapeutic alternative]. / Levo dopa en espasmo hemifacial. Una alternativa terapéutica.

OBJECTIVE: After reviewing the existing literature on the subject, a therapeutic, symptomatic alternative in the treatment of hemifacial spasm is proposed. MATERIAL AND METHOD: Three patients, all with a 5-year history of hemifacial spasm, were given one 25/250-mg tablet of Levodopa/carbidopa every 12 h. In a cross-over study, the patients were their own controls. The initial treatment phase lasted 1 month, at the end of which treatment was suspended. For an equal amount of time, the patients were given a placebo, after which they were again given Levodopa. RESULTS: After a 2-week period of treatment with Levodopa, the symptomatic aspect of the spasm disappeared in the patients. Upon replacing the drug with the placebo, the spasm reappeared. The patients have since been receiving the treatment with Levodopa, one tablet every 12 h, for a period of 4 years and the reduction of the hemifacial spasm has oscillated at 75%. CONCLUSION: We suggest the use of Levodopa/carbidopa in the treatment of hemifacial spasm as a therapeutic alternative. This treatment is within the patients' economic reach and more importantly allows them to once again lead normal lives.

Histamine as a therapeutic alternative in migraine prophylaxis: a randomized, placebo-controlled, double-blind study.

This study was undertaken to test the efficacy of the subcutaneous administration (twice a week) of consecutively increasing doses of histamine (0.1 to 1 ng) in the prophylaxis of migraine, compared to placebo, under a controlled, double-blind, clinical trial for 12 weeks. Sixty patients were selected, under criteria established by the International Headache Society (both sexes, 18 to 65 years of age, a migraine history of more than 1 year, one to six headache attacks per month), having no additional neurological or cardiovascular pathologies, and after a complete clinical and laboratory examination including computer-assisted tomography. Comparison between the groups treated with placebo (n = 30) and histamine (n = 30), on data collected for the 4th, 8th, and 12th weeks of treatment, revealed that histamine exerted a significantly (P < .0001) greater reduction (compared to placebo) in the frequency, intensity, and duration of migraine attacks, as well as on the use of rescue medication. No significant (P > .05) adverse experiences or side effects in either group developed to impede the blinding of the study or the planned order of events. We conclude that the subcutaneous administration of histamine (at very low doses) constitutes a novel and effective therapeutic approach in migraine prophylaxis, aimed at limiting excessive inflammatory responses involved in the pathophysiology of migraine through the activation of H3 receptors.

Inhibition of xanthine oxidase by Puerto Rican plant extracts.

OBJECTIVES: This study was conducted to search for xanthine oxidase inhibitors in natural products obtained from plants collected in Puerto Rico and to assess the influence of these extracts in the prevention of cataractogenesis. BACKGROUND: Allopurinol is currently a xanthine oxidase inhibitor used in the treatment of gout. New alternatives with increased therapeutic activity and less side effects should be investigated. Preclusion of cataractogenesis in diabetic rats is also the focus of this investigation. Natural products in the form of plant extracts from Puerto Rico offer a rich and relatively untapped source for the discovery of new drugs that may address these kind of problems. METHODS: Nineteen collections of Myrtaceae plant extracts were screened for xanthine oxidase inhibition. A spectrophotometrical method was used employing allopurinol as positive control and a blank as negative control. A protocol of the assay with slight modifications was followed from the literature. Two extracts with the highest percentages of xanthine oxidase inhibition were evaluated for possible prevention of cataractogenesis in streptozotocin diabetic rats. The animals were given to drink these plant extracts ad libitum for three months while controls received water. The appearance of cataracts was assessed physically. RESULTS: Two of the nineteen plant extracts showed high inhibition percentages of xanthine oxidase. Eucalyptus deglupta and Syzygium malaccense displayed 51% and 64% inhibitions (IC50 44.5 micrograms/ml and IC50 51 micrograms/ml), respectively. As for the cataractogenesis inhibition, laboratory animals that drank E. deglupta for three months did not develop cataracts. CONCLUSIONS: Two plant extracts provided positive results with varying degrees of inhibition of xanthine oxidase. S. malaccense demonstrated the greatest xanthine oxidase inhibitory activity whereas E. deglupta presented the best finding for cataractogenesis prevention. The procedures used in this investigation are useful for the in vitro screening of xanthine oxidase inhibition and the in vivo evaluation of cataractogenesis prevention.

Endemic plants of Puerto Rico: brine shrimp lethality and antibacterial activity.

A total of 49 endemic plants of Puerto Rico were evaluated for their toxicological and antibacterial activities. The toxicological analysis was conducted with brine shrimp (Artemia salina Leach) lethality bioassay and the antibacterial screening was carried out by means of the agar diffusion test. In the toxicological bioassay, six plant extracts showed LC-50 values below 200 g/ml., indicating the potential presence of bioactive compounds. In the antibacterial screening, over 80% of the plant extracts displayed activity against gram positive bacteria, whereas only 6% of the extracts inhibited the growth of the gram negative bacteria.