Experience of malignancies with oral glucose-lowering drugs in the randomised controlled ADOPT (A Diabetes Outcome Progression Trial) and RECORD (Rosiglitazone Evaluated for Cardiovascular Outcomes and Regulation of Glycaemia in Diabetes) clinical trials.

AIMS/HYPOTHESIS: Observational and mechanistic studies have suggested a possible relationship between treatment with metformin and decreased incidence of cancer in participants with type 2 diabetes. We extracted data for malignancies from the ADOPT (A Diabetes Outcome Progression Trial) and RECORD (Rosiglitazone Evaluated for Cardiovascular Outcomes and Regulation of Glycaemia in Diabetes) randomised controlled clinical trials, in which the efficacy and/or safety of metformin was assessed in comparison with sulfonylureas and rosiglitazone. METHODS: Neoplasm occurrences were collected as adverse events in these studies. We reviewed and re-analysed the individual participant data in both studies for serious adverse events, malignancies reported as adverse events and related neoplasms of special interest. RESULTS: In ADOPT, 50 participants (3.4%) on metformin and 55 (3.8%) on each of rosiglitazone and glibenclamide (known as glyburide in the USA and Canada) developed serious adverse event malignancies (excluding non-melanoma skin cancers). This corresponds to 1.03, 1.12 and 1.31 per 100 person-years, giving hazard ratios for metformin of 0.92 (95% CI 0.63-1.35) vs rosiglitazone and 0.78 (0.53-1.14) vs glibenclamide. In RECORD, on a background of sulfonylurea, 69 (6.1%) participants developed malignant neoplasms in the metformin group, compared with 56 (5.1%) in the rosiglitazone group (HR 1.22 [0.86-1.74]). On a background of metformin, 74 (6.7%) participants in the sulfonylurea group developed malignant neoplasms, compared with 57 (5.1%) in the rosiglitazone group (HR 1.33 [0.94-1.88]). CONCLUSIONS/INTERPRETATION: The malignancy rates in these two randomised controlled clinical trials do not support a view that metformin offers any particular protection against malignancy compared with rosiglitazone. However, they do not refute the possibility of a difference compared with sulfonylureas.

Remarkably enhanced direct dissolution of plutonium oxide in task-specific ionic liquid: insights from electrochemical and theoretical investigations.

The present work envisages an approach for direct dissolution of PuO2 in a task-specific ionic liquid (TSIL). An attractive possibility to electrodeposit plutonium from the mixture of TSIL and PuO2 has been explored further. The carboxyl functional group attached to the TSIL plays a key role in facilitating the dissolution of plutonium ions.

Assessment of metal enrichment and their bioavailability in sediment and bioaccumulation by mangrove plant pneumatophores in a tropical (Zuari) estuary, west coast of India.

Sediment collected from the estuarine mangroves of the Zuari estuary and Cumbharjua canal were analyzed to assess the concentration, contamination and bioavailability of metals. Mangrove pneumatophores were also analyzed to understand the metal bioaccumulation in mangrove plants. The results indicated the variation of metal concentrations in sediment along the estuary was attributed to changing hydrodynamic conditions, type of sediment and metal sources. Further, speciation studies revealed that Fe, Cr, Co, Ni, Cu and Zn were mainly of lithogenic origin and less bioavailable while high Mn content in the sediment raised concerns over its potential mobility, bioavailability and subsequent toxicity. The mangrove plants exhibited difference in metal accumulation due to variations in sediment parameters and metal availability, in addition to difference in plant species and tissue physiology that affect metal uptake. Moreover, the mangrove plants reflected the quality of the underlying sediment and can be used as a potential bio-indicator tool.

Selective recognition of uranyl ions from bulk of thorium(iv) and lanthanide(iii) ions by tetraalkyl urea: a combined experimental and quantum chemical study.

The selective separation of uranyl ions from an aqueous solution is one of the most important criteria for sustainable nuclear energy production. We report herein a known, but unexplored extractant, tetraalkyl urea, which shows supreme selectivity for uranium in the presence of interfering thorium and other lanthanide ions from a nitric acid medium. The structural characterization of the uranyl complex (UO2X2·2L, where X = NO3(-), Cl(-) and Br(-)) by IR, NMR and single crystal X-ray diffraction provides insight into the strong interaction between the uranyl ion and the ligand. The origin of this supreme selectivity for uranyl ions is further supported by electronic structure calculations. Uranyl binding with the extractant is thermodynamically more favourable when compared to thorium and the selectivity is achieved through a combination of electronic and steric effects.

Intranasal sumatriptan for the acute treatment of migraine. International Intranasal Sumatriptan Study Group.

Two double-blind, placebo-controlled, randomised, multicentre, multinational, parallel-group studies were carried out to identify the optimum dose of intranasal sumatriptan for the acute treatment of migraine. Study medication was taken as a single dose through one nostril in the first study, and as a divided dose through two nostrils in the second study. Totals of 245 and 210 patients with a history of migraine were recruited into the one- and two-nostril studies, respectively. In both studies, headache severity had significantly improved at 120 min after doses of 10-40 mg sumatriptan compared to placebo (P < 0.05) and the greatest efficacy rates were obtained with 20 mg sumatriptan. With 20 mg sumatriptan 78% and 74% of patients experienced headache relief in one- and two-nostril studies respectively. Sumatriptan was generally well tolerated, the most frequently reported event being taste disturbance. The results of the two studies are similar and indicate that administering sumatriptan as a divided dose via two nostrils confers no significant advantage over single-nostril administration.

Schistosoma mansoni-New Zealand rabbit model: resistance induced by infection followed by active immunization with protective antigens.

In previous studies, rabbits immunized with adult worm antigens released from fresh adult schistosomes incubated in saline media showed a significant level of protection against challenge parasites. Focusing on the rabbit-Schistosoma mansoni model, concomitant immunity was investigated. A peculiar form of response to cercarial infection was observed: rabbits subjected to percutaneous infection and similar reinfections at different times after primary infection killed schistosomula from the challenge infection as well as established parasites from the primary infection. In this study the challenge infection stimulus was replaced by active immunization with an adult worm-derived protective antigenic mixture. The results show that immunization of New Zealand rabbits with an adult worm antigenic extract is capable of inducing a response that results in a significant reduction of the mean worm burden of the primary infection earlier than did homologous infection, as compared to worm reduction due to a second infection.

Curative and protective activity in rabbits after reinfection with Schistosoma mansoni: a new model of immunity?

New Zealand rabbits were infected on day 1 and challenged on days 15, 30, and 60 with 1,000 Schistosoma mansoni cercariae/animal/infection. Challenged and control rabbits were perfused 60 days after each infection, corresponding to days 75, 90, and 120 after the first exposure. No decrease in number of adult schistosomes occurred in animals reinfected 15 days after primary infection, but, when the rabbits were challenged 30 and 60 days after the first infection, worm burden reduction of 61.4% and 92.6%, respectively, was observed as compared to infection controls. These data indicate that rabbits submitted to reinfection are able to kill the worms from their primary infection, besides being protected against challenge parasites.

Radiological features of pulmonary tuberculosis in patients infected with human immunodeficiency virus.

We tested 120 consecutive admissions with sputum positive pulmonary tuberculosis for antibodies to the human immunodeficiency virus type I (HIV-1). Pre-treatment chest x-ray appearances were recorded. Seventy one patients (59%) were males and 49 (41%) were females. 43 (35.8%) patients were seropositive for HIV, and were all in the age range 16-45 years. The seropositivity for the 56 males and 44 females in the age range 16-45 years were 53 and 26 percent respectively. Atypical x-ray features were found in 21 of 43 cases compared to 15 of 57 referents (p less than 0.025). Radiographic features typical of reactivation pulmonary tuberculosis in the adult were found in 73% and 51% of referents and cases respectively (P less than 0.025). Pulmonary lesions localized to the mid and or lower zones were seen in 20 percent of cases and 3.3% of referents (P = 0.01). Mediastinal and or hilar adenopathy alone or with pulmonary infiltrates occurred more frequently among cases but the results were not significant. Our findings indicate that radiological appearances of pulmonary tuberculosis in patients seropositive for HIV-1 antibodies tend to be atypical in type of lesion and or anatomic distribution, even for patients from communities with high prevalence rates of tuberculosis.

PIP: The authors tested 120 consecutive admissions with sputum positive pulmonary tuberculosis for antibodies to the human immunodeficiency virus type I (HIV-1). Pretreatment chest x-ray appearances were recorded. 71 patients (59%) were males and 49 (41.9%) were females. 43 (35.8%) patients were seropositive for HIV, and were all between the ages of 16-45. The seropositivity for the 56 males and 44 females in this age ranger were 53% and 26%, respectively. Atypical x-ray features were found in 21 of 43 cases compared to 15 of 5 referents (p 0.25). Radiographic features typical of reactivation pulmonary tuberculosis in the adult were found in 73% and 51% of the referents and cases, respectively (p0.025). Pulmonary lesions localized to the middle or lower zones were seen in 20% of cases and 3.3% of the referents (p=0.01). Mediastinal or hilar adenopathy alone or with pulmonary infiltrates occurred more frequently in cases but the results were not significant. These findings indicate that radiological appearances of pulmonary tuberculosis in patients positive for HIV-1 antibodies tend to be atypical in type of lesion and/or anatomic distribution, even for those patients from communities with high prevalence rates of tuberculosis.

Helminth fauna of the golden hamster Mesocricetus auratus in Brazil.

Helminth fauna of conventionally maintained hamsters from institutional animal houses that supply the research community with laboratory animals and from an openly kept control group, randomly purchased in a pet shop in the State of Rio de Janeiro, were evaluated and compared. Necropsied animals from institutional suppliers were infected with the oxyurid nematodes Syphacia criceti and S. mesocriceti and with the cestode Rodentolepis nana; those from the pet shop were infected with S. mesocriceti and R. nana. These are the first morphometric data that are based on Brazilian samples of these species parasitizing hamsters. Mesocricetus auratus is a newly recorded host for S. criceti, previously recovered from Oryzomys subflavus and Calomys callosus in Brazil. The potential of pet and laboratory hamsters in the spreading of helminth infections to humans is also considered.

[Aneurysms of the interatrial septum]. / Aneurismas do septo interauricular.

Atrial septum aneurysms are an uncommon condition, underestimated before the routine use of echocardiography. Their clinical importance has increased after being associated with thromboembolic events. The authors made a review of clinical, diagnostic and therapeutic features of this entity after reporting six clinical cases.

Effects of early life interventions and palatable diet on anxiety and on oxidative stress in young rats.

Early life events can change biochemical, endocrine and behavioral aspects throughout the life of an animal. Since there is a strong relationship between stress, neonatal handling and feeding behavior, the aim of this study was to investigate the effects of these three factors on behavioral parameters (anxiety and locomotion), oxidative stress in brain structures (prefrontal cortex and hippocampus) and on plasma glucose. Nests of Wistar rats were handled (10 min/day), or not (control groups), on days 1-10 after birth. Males from these groups were divided into 4 subgroups: (1) stressed by isolation in childhood (pre-puberty) and with access to a highly palatable diet (2) stressed by isolation and receiving standard lab chow (3) not isolated and receiving a highly palatable diet and (4) not isolated and receiving standard chow. The animals were kept under these conditions for 7 days. Rats receiving the highly palatable diet consumed more food, more calories, gained more weight and had a higher plasma glucose level, but had a lower caloric efficiency than the standard chow groups. Both handling and palatable diet were able to increase food consumption on the first day of isolation. Isolation stress had an anxiogenic effect in the plus maze, which was counteracted by handling. Palatable diet increased time spent in the central area of the open field apparatus and in the open arms of the elevated plus maze, showing an anxiolytic effect. The use of both these conditions, however, does not appear to bring additional protection against the effects of stress during this particular period of life, i.e., pre-puberty. In the prefrontal cortex, handling reduced thiol content and appears to imbalance the antioxidant enzymes system, which is counteracted by a palatable diet. Hippocampus seems to be more sensitive than the prefrontal cortex to early interventions, especially to the highly palatable diet, and both handling and diet appear to imbalance the antioxidant enzyme system. Thus, measurements of antioxidant enzymes activities indicate that handling may endanger some brain structures and that the palatable diet was able to prevent some handling effects on antioxidant enzymes, depending on the brain structure.

Synhimantus (Synhimantus) magnipapillatus n. sp. (Nematoda, Acuarioidea) from the Yellow-crowned Night-heron, Nyctanassa violacea cayennensis (Gmelin) (Aves, Ardeidae).

Synhimantus (Synhimantus) magnipapillatus n. sp., mainly considering the outstanding size of the cervical papillae and the delicate structure of the cephalic cordons, is not related to any other species of the genus, except for S. (S.) laticeps, concerning the similarities regarding the spicules, that justify their comparison.

Subcutaneous sumatriptan in the acute treatment of cluster headache: a dose comparison study. The Sumatriptan Cluster Headache Study Group.

This multicentre, double-blind, randomised, crossover study compared the efficacy, safety and tolerability of subcutaneous sumatriptan (6 mg and 12 mg) with placebo in 134 in-patients with cluster headache. Headache improvement to mild or no pain at 5, 10 and 15 min after treatment was recorded. At 10 min, headache relief was reported by 25% (placebo), 49% (6 mg) and 63% (12 mg) of patients and at 15 min the results were 35% (placebo), 75% (6 mg) and 80% (12 mg) (p < 0.001 for all comparisons with placebo). The 12 mg dose was not significantly better than the 6 mg dose and was associated with more adverse events. The 6 mg dose is therefore recommended for the acute treatment of cluster headache.

Helminth parasites of conventionally maintained laboratory mice.

The spectrum of intestinal parasites present in the Swiss Webster, C57B1/6 and DBA/2 mice strains from different animal houses was identified and prevalences compared. Three parasites were observed during the course of this study, namely the cestode Vampirolepis nana (Siebold, 1852) Spasskii, 1954 (= Hymenolepis nana) and the nematodes Aspiculuris tetraptera (Nitzsch, 1821) Schultz, 1924 and Syphacia obvelata (Rudolphi, 1802) Seurat, 1916. The scope of this investigation has been widened to also include morphometric data on the parasites, to further simplify their identification, since the presence of helminths in laboratory animals is regarded as a restricting factor for the proper attainment of experimental protocols.

Worm burdens in outbred and inbred laboratory rats with morphometric data on Syphacia muris (Yamaguti, 1935) Yamaguti, 1941 (Nematoda, Oxyuroidea).

Syphacia muris worm burdens were evaluated in the rat Rattus norvegicus of the strains Wistar (outbred), Low/M and AM/2/Torr (inbred), maintained conventionally in institutional animal houses in Brazil. Morphometrics and illustration data for S. muris recovered from Brazilian laboratory rats are provided for the first time since its proposition in 1935.

Helminth parasites of conventionally maintained laboratory mice--II. Inbred strains with an adaptation of the anal swab technique.

Worm burdens recovered from inbred mice strains, namely C57Bl/6, C57Bl/10, CBA, BALB/c, DBA/2 and C3H/He, conventionally maintained in two institutional animal houses in the State of Rio de Janeiro, RJ, Brazil, were analyzed and compared, regarding their prevalences and mean intensities. Three parasite species were observed: the nematodes Aspiculuris tetraptera, Syphacia obvelata and the cestode Vampirolepis nana. A modification of the anal swab technique is also proposed for the first time as an auxiliary tool for the detection of oxyurid eggs in mice.

On two nematodes from Brazilian birds and description of a new species (Acuarioidea, Schistorophinae) parasitizing Laterallus viridis (Müller, 1776) (Gruiformes, Rallidae).

The present paper reports acuarioid nematodes recovered from avian hosts. A new species of the genus Schistorophus Railliet, 1916 is proposed based mainly on findings referring to ptilina, spicules and vagina. Ancyracanthopsis coronata (Molin, 1860) Chabaud & Petter, 1959 is referred again in Brazil since its proposition in 1860, from specimens recovered from a Brazilian bird. A revised key to the species of the genus Schistorophus is also presented.