Glycogen stores are impaired in hypothalamic nuclei of rats malnourished during early life.

Perinatal nutrition has persistent influences on neural development and cognition. In humans and other animals, protein malnutrition during the perinatal period causes permanent changes, inducing to adulthood metabolic syndrome. Feeding is mainly modulated by neural and hormonal inputs to the hypothalamus. Hypothalamic glycogen stores are a source of glucose in high energetic demands, as during development of neural circuits. As some hypothalamic circuits are formed during lactation, we studied the effects of malnutrition, during the first 10 days of lactation, on glycogen stores in hypothalamic nuclei involved in the control of energy metabolism. Female pregnant rats were fed ad libitum with a normal protein diet (22% protein). After delivery, each dam was kept with 6 male pups. During the first 10 days of lactation, dams from the experimental group received a protein-free diet and the control group a normoprotein diet. By post-natal day 10 (P10), glycogen stores were very high in the arcuate nucleus and median eminence of control group. Glycogen stores decreased during development. In P20 control animals, glycogen stores were lower when compared to P10 control animals. Animals submitted to malnutrition presented a staining even lower than control ones. After P45, it was difficult to determine differences between control and diet groups because glycogen stores were reduced. We also showed that tanycytes were the cells presenting glycogen stores. Our data reinforce the concept that maternal nutritional state during lactation may be critical for neurodevelopment since it resulted in a low hypothalamic glycogen store, which may be critical for establishment of neuronal circuitry.

Invasive cervical cancer and smoking in Latin America.

A case-control study of 667 patients with invasive squamous cell carcinoma of the cervix and 1,430 controls from four Latin American countries showed an age-adjusted relative risk (RR) of 1.2 [95% confidence interval (CI) = 1.0-1.4] for women who had ever smoked, with risk rising to 1.7 (95% CI, 0.8-3.6) for women who smoked greater than or equal to 30 cigarettes per day. The associations were practically eliminated after adjustment for the number of sexual partners and alcohol consumption, probably a surrogate for an unidentified life-style risk factor. Some excess risk persisted among women who smoked for extended periods (RR = 1.5 for greater than or equal to 40 yr), as well as those who began smoking at older ages (RR = 1.7 for greater than 30 yr), which suggests a late-stage effect. In addition, among women who tested positive for human papillomavirus (HPV) type 16 or 18 by filter in situ hybridization, there was an increased risk for women who had ever smoked and a dose-response relationship with the number of cigarettes smoked (adjusted RRs compared with HPV-negative nonsmokers = 5.0 for HPV-positive nonsmokers, 5.5 for less than 10 cigarettes/day, and 8.4 for greater than or equal to 10 cigarettes/day). In contrast, HPV-negative women had no increased risk associated with smoking. These results, from a high-incidence area where intensive smoking among women is still relatively rare, suggest that smoking has a limited effect on cervical cancer risk, possibly only among women with specific types of HPV.

A case-control study of serum folate levels and invasive cervical cancer.

Although small intervention trials have suggested that folate supplementation reduces cervical dysplasia, the association of blood folate concentrations with invasive cervical cancer risk has not been investigated in well-controlled epidemiological studies. A study was conducted with newly diagnosed Stage I and II invasive cervical cancer cases and controls in 4 Latin American countries. Ninety-five% of subjects donated blood samples, resulting in 330 case and 565 control serum samples analyzed for folate concentrations by radioassay. Cases did not differ significantly from controls in mean levels of folate (5.00 and 4.90 ng/ml, respectively). No associations were observed between quartiles of serum folate and risk of cervical cancer after adjustment for other risk factors, and no interactions with established risk factors were observed. Folate levels were also unrelated to risk among women who might have compromised folate status because of recent or extended oral contraceptive usage or multiple pregnancies. Further, mean levels of folate were similar by stage of disease, arguing against an effect of disease progression on serum values. These results do not support a role for serum folate in the etiology of invasive cervical cancer.

Sonochemical assisted synthesis of SrFe12O19 nanoparticles.

We present the synthesis of M-type strontium hexaferrite by sonochemistry and annealing. The effects of the sonication time and thermal energy on the crystal structure and magnetic properties of the obtained powders are presented. Strontium hexagonal ferrite (SrFe12O19) was successfully prepared by the ultrasonic cavitation (sonochemistry) of a complexed polyol solution of metallic acetates and diethylene glycol. The obtained materials were subsequently annealed at temperatures from 300 to 900 °C. X-ray diffraction analysis shows that the sonochemical process yields an amorphous phase containing Fe(3+), Fe(2+) and Sr(2+) ions. This amorphous phase transforms into an intermediate phase of maghemite (γ-Fe2O3) at 300 °C. At 500 °C, the intermediate species is converted to hematite (α-Fe2O3) by a topotactic transition. The final product of strontium hexaferrite (SrFe12O19) is generated at 800 °C. The obtained strontium hexaferrite shows a magnetization of 62.3 emu/g, which is consistent with pure hexaferrite obtained by other methods, and a coercivity of 6.25 kOe, which is higher than expected for this hexaferrite. The powder morphology is composed of aggregates of rounded particles with an average particle size of 60 nm.

Cutaneous pythiosis in a donkey (Equus asinus) in Brazil.

Our study describes the clinical, epidemiologic, pathologic, immunohistochemical, and molecular aspects PCR of a case of cutaneous pythiosis in a donkey (Equus asinus) from Brazil. During a dry period, the animal grazed for 4 months around a pond where the vegetation remained green. Skin lesions were nodular, multifocal, and disseminated, mainly involving the legs, ventral chest, and mammary gland. On cut surface, there were multifocal to coalescent discrete yellow foci, and occasional small cavitations with a few kunkers. Ulcerative nodular pyogranulomatous and eosinophilic dermatitis with folliculitis and furunculosis were observed histologically. Hyphae were observed in sections stained with Gomori methenamine silver. Immunohistochemistry with Pythium insidiosum antibodies yielded strong immunostaining of hyphae. P. insidiosum DNA was extracted from tissues in paraffin blocks by amplification of a fragment of 105 bp, which targets the 5.8S ribosomal gene. After the diagnosis of pythiosis, the larger skin lesions were excised and treated as second intention healing wounds, which were completely healed 30 days after resection. Small skin lesions regressed spontaneously in ~60 days. The granulomatous inflammation and outcome of the disease in this donkey were similar to cases of pythiosis in cattle.

Vasodilator activity of the aqueous extract of Viscum album.

The aqueous extract of Viscum album leaves showed a significant coronary vasodilator activity on the Langendorff's isolated and perfused heart model. The data obtained suggest that the aqueous extract of V. album contains some biologically active principles that may act as inducers of the nitric oxide/soluble guanylate cyclase pathway.

Screening for cervical cancer in Latin America: a case-control study.

The beneficial effect of cervical cytology in reducing the incidence of invasive cervical cancer is well accepted, but many issues regarding specific patterns of screening remain to be resolved, and preventive programmes need to be adapted to regional characteristics. In a case-control study conducted in Latin America, we investigated cytological screening histories of 759 cases of invasive cervical cancer and 1430 controls, with participation rates of 99% and 96%, respectively. Fifty per cent of the cases and 29% of the controls reported never having been screened. Screening was less common among older, less educated and less parous women; non-users of oral contraceptives and women without histories of venereal diseases. There was also evidence that older women and those with multiple partners had longer intervals between examinations. The relative risk (RR) associated with no prior screening was approximately 3 and was not modified by other risk factors. Women reporting a Pap smear within 24-47 months before interview had the same RR as those examined within 12-23 months. Women tested longer ago had higher risks, but still much lower than women never examined. There was evidence that one examination is associated with less reduction in risk than two, regardless of the interval since last Pap smear. Screening appeared to reduce risk of both squamous cell carcinomas and adenocarcinomas. As expected, cases presenting at advanced stages were less likely to have been screened and reported longer intervals since their last examination. These results support the need to concentrate limited resources in the groups that need screening most, mainly older and less educated women who have never been screened.

Oral contraceptive use and risk of invasive cervical cancer.

A case-control study of 759 invasive cervical cancer patients and 1430 controls in Panama, Costa Rica, Colombia and Mexico enabled an evaluation of risk in relation to oral contraceptive use. Overall use was associated with a 21% nonsignificant elevation in risk, with some further increases in risk for more extensive durations of use. Although risks were similar for recent and non-recent users (RRs = 1.3 versus 1.2), recent long-term users were at highest risk (RR for 5+ years use = 1.7, 95% Cl 1.1-2.6). Relationships were similar for women with and without a recent Pap smear, arguing against detection bias. There was little evidence that other risk factors, including smoking and detection of human papillomaviruses (HPV), altered the effects of oral contraceptives. The risk associated with oral contraceptives was significantly increased for adenocarcinomas (RR = 2.2), whereas for squamous cell tumours the effect was minimal (RR = 1.1). These results provide some support for an adverse effect of oral contraceptives on cervical cancer risk, although possibly limited only to a subpopulation of cases.

Eye enucleation alters intracellular distribution of NO synthase in the superior colliculus.

We investigated the role of retinotectal projections on the distribution of nitric oxide synthase (NOS) in the retinoceptive layers of the rat superior colliculus (SC) using histochemical methods. Rats enucleated at birth showed no alteration in the temporal pattern of NOS expression. There was, however, a dramatic change in the NADPH-diaphorase staining pattern of NOS-positive cells. NOS was absent from the distal portions of the dendritic trees of the deafferented SC. Nevertheless, staining the dendritic trees of these cells with Lucifer yellow showed that they were not morphologically different from those of the ipsilateral SC of monoenucleated animals. The same results were obtained when enucleation was performed in adult rats. We conclude that NOS intracellular distribution in the SC cells can be regulated by retinotectal projections in both developing and adult animals.

Phase II trial of carboplatin or iproplatin in cervical cancer.

From July 1984 to November 1987, 89 patients with recurrent measurable squamous-cell cancer of the uterine cervix were randomized in a single institution to receive treatment with either carboplatin (CBDCA) or iproplatin (CHIP). Objective response rates were similar: 2 complete regressions (CRs) and 10 partial regressions (PRs) were recorded both in the 46 evaluable patients treated with CBDCA (response rate, 26.1%; 95% confidence interval, 15-41%) and in the 40 evaluable patients treated with CHIP (response rate, 30%; 95% confidence interval, 17-47%). The median duration of response was 5.5 months for CBDCA and 6 months for CHIP; the median survival was 7.5 and 7.6 months, respectively. Both drugs were given in an outpatient setting and myelosuppression (thrombocytopenia) was the predominant toxicity. Analysis of all toxic events yielded additional interesting observations: the occurrence of moderate to severe platelet nadirs beyond cycle 1 was confined to CHIP, a higher incidence of gastrointestinal toxicity during treatment with CHIP, and five moderate to severe complaints of asthenia (recorded as neurologic events) during CHIP therapy versus only one during treatment with CBDCA. Because of its antitumor activity and its toxicologic advantage, a future role for CBDCA in the treatment of cervical cancer appears likely.

Morphology of NADPH-diaphorase-positive cells in the retinoceptive layers of the developing rat superior colliculus.

We have used diaphorase histochemistry to study the morphology of cells expressing nitric oxide synthase in the superficial layers of the superior colliculus of developing and adult rats. The nitric oxide synthase-positive cells showed a Golgi-like morphology and were classified according to the cell types identified by several authors using the Golgi method. The first nitric oxide synthase-positive cells appeared at postnatal day 7 and the number of stained cells increased progressively reaching a maximum at postnatal day 15. The poor staining of the dendritic tree and cell bodies in animals younger than postnatal day 15 allowed no unambiguous identification of the different cell types before that age. At postnatal day 15, based on cell soma and dendritic morphology, we have found that the following cell types express nitric oxide synthase: marginal, horizontal, narrow and wide-field vertical and stellate. In the adult, the same cell types were found to express nitric oxide synthase but the staining intensity and frequency of each cell type was different from the developing animal. Our results show that cells expressing nitric oxide synthase constitute a subpopulation of neurons in which all cell types are represented. Furthermore, our observations of nitric oxide synthase expression by collicular cells starting by the end of the first postnatal week and reaching a maximum by postnatal day 15 parallels the functional development of the retino-collicular and cortico-tectal projections and suggest that nitric oxide synthase-positive cells might be involved in this process.

Expression of nitric oxide synthase in the developing rat hippocampus.

Nicotinamide adenine dinucleotide phosphate-diaphorase (NADPH-d) histochemistry was used to study the development of neurons synthesizing nitric oxide (NO) in the postnatal rat hippocampus. We show that NADPH-d reactive somata and processes are present from the day of birth until adulthood in the Ammon's horn. The dentate gyrus, however, has a more delayed period of nitric oxide synthase (NOS) expression with the staining appearing only by the end of the first postnatal week. Our results suggest that the time course of NOS expression correlates with the developmental sequence of events described in the hippocampus and that NO could be involved in the development of connections in this structure.

[Psychoanalysis, individualistic value shaping, and social ethics]. / Psicanalise, configuracao individualista de valores e etica do social.

Refuting the view now prevailing in social anthropology, the article seeks to offer a new outlook on relations between psychoanalysis and the individualistic shaping of values that characterizes modern Western society. According to current social anthropology, psychoanalysis embodies the promise of recouping a wholeness lost as a result of the world's process of de-sanctification. The self is seen as constituting this new wholeness value, while psychoanalysis, insofar as it proposes redemption through the self, is viewed as a modern religion with individualistic effects. In questioning this vision, the article offers as a counterpoint the idea that the Lacanian formalization of the subconscious through symbolic structure overcomes the dichotomy between subject and society. This leads Lacan to assert that analysis should lead the subject to dedicate his or herself to guaranteeing the workings of the great Other, which is understood to mean that psychoanalysis should lead the subject to assume his or her responsibility for the workings of the symbolic structure.

Undernutrition during early life alters neuropeptide Y distribution along the arcuate/paraventricular pathway.

Perinatal nutrient restriction exerts profound influences on brain development. Animals that suffer undernutrition during lactation also display impaired weight gain. Feeding behavior is mainly modulated by neural and hormonal inputs to the hypothalamus. The arcuate-paraventricular neuropeptidergic Y pathway has a prominent role in appetite regulation. The aim of this work was to study the effects of protein undernutrition during lactation on this hypothalamic pathway. We used rats from 5 to 60 postnatal (P) days whose dams were fed a 0% protein diet (PFG) or a normoprotein diet (CG) from P1 to P10. To reproduce the same amount of calorie ingested by the PFG we used an underfed group (UFG). Immunohistochemistry was performed to assess neuropeptide Y (NPY) distribution in the arcuate, periventricular and paraventricular nuclei. Our results showed a NPY immunostaining peak at P10 in all nuclei in CG animals. In UFG animals this peak was observed by P15, while, in the PFG animals only by P20. Our results suggest that the neuropeptidergic arcuate-paraventricular pathway suffered a delay in NPY distribution in undernourished animals, particularly those fed a 0% protein diet, reflecting an effect on this pathway maturation that could explain previously reported alterations on feeding behavior in these animals.

[Clinical trial comparing efficacy and safety of four highly active antiretroviral therapy (HAART) in antiretroviral-naive treatment with advanced HIV infection]. / Ensayo clínico comparativo de eficacia y seguridad de cuatro pautas de tratamiento antirretroviral de alta eficacia (TARGA) en pacientes naive con infección por VIH avanzada.

BACKGROUND: Comparison of efficacy and safety of four highly active antiretroviral therapy regimens (HAART) including two nucleoside analogues (NA) and a protease inhibitor (PI) in HIV positive patients with advanced infection and antiretroviral naive. PATIENTS AND METHODS: Multicenter, randomized and open labeled clinical trial in ten community hospitals of Castilla-La Mancha and Madrid. Regimen 1 contains zidovudine (AZT), lamivudine (3TC) and indinavir (IDV) regimen 2 includes AZT, 3TC and ritonavir (RTV), regimen 3 was didanosine (DDI), estavudine (D4T) and IDV, and regimen 4 included DDI, D4T and RTV. Decrease in viral load of HIV (VC) has been assessed as primary endpoint and as secondary one, the increase of the numbers of CD4 lymphocytes, percentage of disease progression, adverse reactions and adherence. Measurements were made at baseline visit and at 6, 12, 24, 36 and 48 weeks. RESULTS: A total of 98 patients with a mean baseline CD4 count of 122 x 10(6)/l (range of 5-340) and a baseline viral load of 5.1 log copies/ml were included. At 48 weeks, a mean increase of the CD4 and decrease of the viral load without significant difference between the 4 regimens (103 cells/2.62 log in regimen 1; 169 cells/2.86 log in regimen 2; 171 cells/2.56 log in regimen 3 and 141 cells/1.71 log in regimen 4) were observed in the analysis of the patients in treatment. Treatment was discontinued due to adverse reactions: 24% in regimen 1, 48% in regimen 2, 26% in regimen 3 and 32% in regimen 4, without significant difference. Analyzing by PI groups, 41% of the patients with RTV and 25% of those with IDV discontinued treatment due to adverse effects. There was withdrawal from treatment due to disease progression in 7% of the RTV patients and in 9% of IDV patients. CONCLUSIONS: In the HIV positive patients with advanced infection, efficacy between the four regimens of HAART is similar, but there is a tendency to require more withdrawal due to adverse effects in the RTV group than in those of IDV, the two used as single PI.

Myelin basic protein accumulation is impaired in a model of protein deficiency during development.

During the development of the central nervous system (CNS) there is a great possibility of permanent effects in consequence of environmental disturbances. Nutritional deficiency is one of the factors that impair the normal CNS formation. In general, the protein deficiency evokes, beyond the damages in the maturation of nervous system, several consequences in body growth, biochemical maturation, motor function and the major cognitive functions. These effects were observed in undernourished children all over the world. Even in a restricted period, the malnutrition status may evoke permanent impairments in feeding behavior and in metabolism. Rats submitted to malnutrition during development, showed a marked decrease in the number of myelinated fibers. This condition may reflect a failure in the beginning of the wrapping of axons by oligodendroglial processes and/or a delay in the myelin synthesis. Myelin basic protein (MBP) is an intracellular oligodendrocyte protein that is directly related to the formation of the myelin sheath. In this study we verified the temporal pattern of MBP expression, by immunohistochemical and immunoblotting analyses, in a model of protein malnutrition induced during the first half of the lactation period. We showed that MBP expression was impaired in our malnutrition model and that some of the effects were maintained in adulthood, with possible consequences in the maturation of myelin sheath.

Developmental changes of nitric oxide synthase in the rat superior colliculus.

We used the activity of nicotinamide adenine dinucleotide phosphate diaphorase (NADPH-d) to detect the presence of nitric oxide synthase (NOS) in the developing rat superior colliculus. Our results showed that NOS is present in cells and neuropil in the developing and adult rat superior colliculus. The first NOS-positive cells were detected at postnatal day 7 and were weakly stained. During the following days the number of stained cells increased markedly, reaching a peak by postnatal day 15, coinciding with the time of eye opening in the rat. By the end of the third postnatal week, both the number and intensity of stained cells showed an adult-like pattern. We conclude that NOS expression lags behind the initial period of reorganization of the retinotectal projection. However, NOS activity could be involved in the subsequent synaptic remodeling and plasticity of the retinocollicular projection.

Hypothalamic nuclei nitric oxide synthase expression in rats malnourished during early lactation period.

In humans and other animals, it has been shown that protein malnutrition during the prenatal period leads to permanent changes, which in adulthood may cause chronic diseases. Molecules involved in the control of energy metabolism could be targets to alterations caused by nutritional status. Some hypothalamic nuclei as the paraventricular (PVN), ventro-medial and arcuate are related to energy metabolism regulation. Orexigenic and anorexigenic molecules are involved in this regulation. Some studies have showed that these nuclei present nitric oxide synthase (NOS) and that it is increased in obese rats. Recently it had been shown that rats malnourished during the lactation period presented metabolic alterations that persist in adulthood. The aim of this work was to study the expression of NOS in hypothalamic nuclei of rats submitted to malnutrition during the early lactation period. Rats from post-natal day (P10) to P90 were used. Control dams were fed with regular chow pellets and diet dams were fed with protein-free chow pellets during the first 10 days of lactation. NADPH-diaphorase or immunostaining techniques were used to access NOS expression in hypothalamic nuclei. Our results show a delay in NOS expression in the PVN and VMH of malnourished rats. It may affect the development of the hypothalamic circuitry, leading to a metabolic imprinting.