Neonatal Handling Reduces Renal Function in Adult Rats

Background/Aims: To evaluate the effects of neonatal handling on hydroelectrolytic balance in adult rats. Methods: The litters were divided into two groups: nonhandled and handled. The procedure consisted of handling the pups for 1 min/day in the first 10 days postnatally. When adults, animals had their body weight verified and were housed in individual metabolic cages. After a 24-hour period, urine samples were collected and the urinary and water intake volumes measured. Blood samples to determine osmolality, aldosterone, corticosterone, angiotensin II, creatinine, urea, sodium and potassium levels were collected. The kidneys were removed for histological assessment. Urinary osmolality, sodium, urea and creatinine were also measured and the creatinine clearance (CC) calculated. Results: No difference between groups was found in the body weight. Handled animals showed a reduction in the total kidney wet weight, water intake, urinary volume, CC, plasma angiotensin II, corticosterone and aldosterone when compared to the nonhandled and an increase in the urinary osmolality and sodium excretion fraction. No differences in serum potassium and no evidence of structural changes were demonstrated by histological analysis. Conclusion: Neonatal handling induced long-lasting effects decreasing renal function without evidence of kidney structural changes. Copyright (c) 2009 S. Karger AG, Basel

Renal structure and function evaluation of rats from dams that received increased sodium intake during pregnancy and lactation submitted or not to 5/6 nephrectomy

Adult rats submitted to perinatal salt overload presented renin-angiotensin system (RAS) functional disturbances. The RAS contributes to the renal development and renal damage in a 5/6 nephrectomy model. The aim of the present study was to analyze the renal structure and function of offspring from dams that received a high-salt intake during pregnancy and lactation. We also evaluated the influence of the prenatal high-salt intake on the evolution of 5/6 nephrectomy in adult rats. A total of 111 sixty-day-old rat pups from dams that received saline or water during pregnancy and lactation were submitted to 5/6 nephrectomy (nephrectomized) or to a sham operation (sham). The animals were killed 120 days after surgery, and the kidneys were removed for immunohistochemical and histological analysis. Systolic blood pressure (SBP), albuminuria, and glomerular filtration rate (GFR) were evaluated. Increased SBP, albuminuria, and decreased GFR were observed in the rats from dams submitted to high-sodium intake before surgery. However, there was no difference in these parameters between the groups after the 5/6 nephrectomy. The scores for tubulointerstitial lesions and glomerulosclerosis were higher in the rats from the sham saline group compared to the same age control rats, but there was no difference in the histological findings between the groups of nephrectomized rats. In conclusion, our data showed that the high-salt intake during pregnancy and lactation in rats leads to structural changes in the kidney of adult offspring. However, the progression of the renal lesions after 5/6 nephrectomy was similar in both groups.

Identification of genes differentially expressed in a strain of the mold Aspergillus nidulans carrying a loss-of-function mutation in the palA gene

To identify genes differentially expressed in a strain of the mold Aspergillus nidulans carrying a loss-of-function mutation in palA, a gene in the pH-responsive signal transduction pathway, suppression subtractive hybridization was performed between RNA isolated from the biA1 and biA1 palA1 strains grown under limiting inorganic phosphate at pH 5.0. We have identified several genes upregulated in the biA1 palA1 mutant strain that play important roles in mitotic fidelity, stress responses, enzyme secretion, signal transduction mechanisms, development, genome stability, phosphate sensing, and transcriptional regulation among others. The upregulation of eight of these transcripts was also validated by Northern blot. Moreover, we show that a loss of function mutation in the palA gene drastically reduced the neutral sugar content of the acid phosphatase PacA secreted by the fungus A. nidulans grown at pH 5.0 compared with a control strain.

Evaluation of Sexual Function in Brazilian Pregnant Women

The objective of the present study was to evaluate the sexual function of pregnant women and to identify the potential variables associated with it. The study was conducted on 137 low-risk, sexually active pregnant women who filled out the Female Sexual Function Index (FSFI) questionnaire. Although 61% of the women assessed presented an FSFI score 26.5, they declared that they were satisfied with the emotional proximity to their partner, with their relationship, and with their sex life. A positive association was detected between sexual dysfunction and gestational age and a report of urinary incontinence and excessive weight gain in the current pregnancy.

Both a combined oral contraceptive and depot medroxyprogesterone acetate impair endothelial function in young women

Background: The study was conducted to determine whether the use of a combined oral contraceptive (COC) or depot medroxyprogesterone acetate (DMPA) interferes with endothelial function. Study Design: The study was conducted on 100 women between the ages of 18 and 30 years. Fifty women had not used hormonal contraception (control group) for at least 12 months, 25 were current users of a COC (ethinylestradiol 30 mcg+levonorgestrel 150 mcg) and 25 were current users of DMPA (150 mg) for at least a 6-month period. All women were evaluated for brachial flow-mediated dilation (FMD), intima-media thickness, carotid distensibility and stiffness index, arterial pressure, body mass index, waist circumference, heart rate and lipid profile. Results: A significant difference in FMD was observed between the COC and control groups (6.4 +/- 2.2% vs. 8,7 +/- 3.4%, p<.01) and between the DMPA and control groups (6.2 +/- 2.1% vs. 8.7 +/- 3.4%, p<.01). The DMPA group had lower values of total cholesterol (TC) and low-density lipoprotein (LDL-C) than COC users and the control group (TC: DMPA=139.9 +/- 21.5 mg/dL vs. controls=167.1 +/- 29.2 mg/dL vs. COC=168.2 +/- 37.5. p=.001; LDL-C: DMPA-85.3 +/- 20.1 mg/dL vs. controls=102 +/- 24.5 mg/dL vs. COC=106.7 +/- 33.3 mg/dL, p=.01). The control group had higher levels of high-density lipoprotein (HDL-C) than the DMPA and COC groups (controls=52.4 +/- 14.1 mg/dL vs. DMPA=42.2 +/- 7.2 mg/dL vs. COC=45.4 +/- 9.1 mg/dL, p=.001). No significant differences were observed regarding the other variables. Conclusions: FMD was lower among COC and DMPA users, Suggesting that these hormonal contraceptives may promote endothelial dysfunction. (C) 2009 Elsevier Inc. All rights reserved.

Sonographic evaluation of endothelial function in letrozole and tamoxifen users

Objectives: Studies have shown that women previously treated for breast cancer present fewer cardiovascular events, indicating a possible protective effect of tamoxifen treatment. The effects of these aromatase inhibitors on cardiovascular protection remain controversial. The aim of this study was to compare some cardiovascular risk markers among breast cancer survivors following treatment with tamoxifen group (TMXg), letrozole group (LTZg) or no endocrine treatment group (NETg). Methods: A total of 103 breast cancer survivors: 35 using TMXg, 34 using letrozole group (LTZg) and 34 using no endocrine treatment group (NETg) were evaluated. Ultrasonographic evaluation of brachial artery flow-mediated dilation (FMD), carotid intima-media thickness (IMT) and stiffness index (beta); blood total cholesterol, HDL and triglycerides were assessed. Results: All three groups presented similar values of HDL and IMT. TMXg showed the lowest total cholesterol (219.29 +/- 36.31 mg/dL vs. 250.59 +/- 38.37 mg/dL vs. 245.09 +/- 35.35 mg/dL; TMXg vs. LTZg vs. NETg, respectively; p < 0.01-ANOVA), the highest triglycerides (139.34 +/- 41.82 mg/dL vs. 111.35 +/- 28.22 mg/dL vs.122.09 +/- 33.42 mg/dL; p < 0.01), the highest FMD (6.32 +/- 2.33% vs. 4.10 +/- 2.06% vs. 4.66 +/- 2.52%; p < 0.01) and the lowest stiffness index (beta) (5.08 +/- 1.68 vs. 6.28 +/- 1.75 vs. 5.99 +/- 1.86; p=0.01). LTZg did not differ significantly from NETg on any evaluated parameter. Conclusions: We did not observe any effect of LTZg on the evaluated cardiovascular risk parameters compared to NETg. As such, the observed difference on lipid values, stiffness index (beta) and FMD between women receiving tamoxifen anti letrozole might be best attributed to the beneficial effect of tamoxifen than to a detrimental effect of letrozole. (C) 2008 Elsevier Ireland Ltd. All rights reserved.

Modulation of effective connectivity during emotional processing by Delta(9)-tetrahydrocannabinol and cannabidiol

Cannabis sativa, the most widely used illicit drug, has profound effects on levels of anxiety in animals and humans. Although recent studies have helped provide a better understanding of the neurofunctional correlates of these effects, indicating the involvement of the amygdala and cingulate cortex, their reciprocal influence is still mostly unknown. In this study dynamic causal modelling (DCM) and Bayesian model selection (BMS) were used to explore the effects of pure compounds of C. sativa [600 mg of cannabidiol (CBD) and 10 mg Delta(9)-tetrahydrocannabinol (Delta(9)-THC)] on prefrontal-subcortical effective connectivity in 15 healthy subjects who underwent a double-blind randomized, placebo-controlled fMRI paradigm while viewing faces which elicited different levels of anxiety. In the placebo condition, BMS identified a model with driving inputs entering via the anterior cingulate and forward intrinsic connectivity between the amygdala and the anterior cingulate as the best fit. CBD but not Delta(9)-THC disrupted forward connectivity between these regions during the neural response to fearful faces. This is the first study to show that the disruption of prefrontal-subocrtical connectivity by CBD may represent neurophysiological correlates of its anxiolytic properties.

Involvement of the central nervous system in the chronic form of Chagas` disease

Background and purpose: Apart from the central nervous system parasitic invasion in chagasic immunodeficient patients and strokes due to heart lesions provoked by the disease, the typical neurological syndromes of the chronic phase of Chagas` disease (CD) have not yet been characterized, although involvement of the peripheral nervous system has been well documented. This study aims at investigating whether specific signs of central nervous system impairment might be associated with the disease. Methods: Twenty-seven patients suffering from the chronic form of Chagas` disease (CCD) and an equal number of controls matched for sex, age, educational and socio-cultural background, and coming from the same geographical regions, were studied using neurological examinations, magnetic resonance images, and electroencephalographic frequency analysis. Results: Nineteen patients were at the stage A of the cardiac form of the disease (without documented structural lesions or heart failure). Dizziness, brisk reflexes, and ankle and knee areflexia were significantly more prevalent in the patients than in the controls. The significant findings in quantitative electroencephalogram were an increase in the theta relative power and a decrease in the theta dominant frequency at temporal-occipital derivations. Subcortical, white matter demyelination was associated with diffuse theta bursts and theta-delta slowing in two patients. Conclusions: Our findings suggest a discrete and unspecific functional cortical disorder and possible white matter lesions in CD. The focal nervous system abnormalities in CD documented here did not seem to cause significant functional damage or severely alter the patient`s quality of life. (C) 2008 Elsevier B.V. All rights reserved.

Aspirin prevents diabetic oxidative changes in rat lacrimal gland structure and function

The aim of this study is to evaluate whether aspirin reduces Diabetis Mellitus (DM) oxidative damage in the lacrimal gland (LG), and ocular surface (OS). Ten weeks after streptozotocin induced DM and aspirin treatment, LG and OS of rats were compared for tear secretion, hidtology, peroxidase activity, and expression of uncoupling proteins (UCPs). DM reduction of tear secretion was prevented by aspirin (P < 0.01). Alterations of LG morphology and increased numbers of lipofucsin-like inclusions were observed in diabetic but not in aspirin-treated diabetic rats. Peroxidase activity levels were higher and UCP-2 was reduced in DM LG but not in aspirin treated (P = 0.0025 and P < 0.05, respectively). The findings prevented by aspirin indicate a direct inhibitory effect on oxidative pathways in LG and their inflammatory consequences, preserving the LG structure and function against hyperglycemia and/or insulin deficiency damage.

The aging lacrimal gland: Changes in structure and function

The afferent nerves of the cornea and conjunctiva, efferent nerves of the lacrimal gland, and the lacrimal gland are a functional unit that works cooperatively to produce the aqueous component of tears. A decrease in the lacrimal gland secretory function can lead to dry eye disease. Because aging is a risk factor for dry eye disease, study of the changes in the function of the lacrimal gland functional unit with age is important for developing treatments to prevent dry eye disease. No one mechanism is known to induce the changes that occur with aging, although multiple different mechanisms have been associated with aging. These fall into two theoretical categories: programmed theories of aging (immunological, genetic, apoptotic, and neuroendocrine) and error theories of aging (protein alteration, somatic mutation, etc). Lacrimal glands undergo structural and functional alteration with increasing age. In mouse models of aging, it has been shown that neural stimulation of protein secretion is an early target of aging, accompanied by an increase in mast cells and lipofuscin accumulation. Hyperglycemia and increased lymphocytic infiltration can contribute to this loss of function at older ages. These findings suggest that an increase in oxidative stress may play a role in the loss of lacrimal gland function with age. For the afferent and efferent neural components of the lacrimal gland functional unit, immune or inflammatory mediated decrease in nerve function could contribute to loss of lacrimal gland secretion with age. More research in this area is critically needed.

Aestivation in the South American lungfish, Lepidosiren paradoxa: Effects on cardiovascular function, blood gases, osmolality and leptin levels

The African (Protopterus sp.) and South American lungfish (Lepidosiren paradoxa) inhabit shallow waters, that seasonally dry out, which induces aestivation and cocoon formation in Protopterus. Differently, L. paradoxa has no cocoon, and it aestivates in a simple burrow. In water PaCO(2) is 21.8 +/- 0.4 mmHg (mean values +/- S.E.M.; n = 5), whereas aestivation for 20 days increased PaCO(2) to as much as 37.6 +/- 2.1 mmHg, which remained the same after 40 days (35.8 +/- 3.3 mmHg). Concomitantly. the plasma [HCO(3)(-)]-values for animals in water were 22.5 +/- 0.5 mM, which after 20 days increased to 40.2 +/- 2.3 mM and after 40 days to 35.8 +/- 3.3 mM. Initially in water, PaO(2) was 87.7 +/- 2.0 mmHg, but 20 days in aestivation reduced the value to 80.5 +/- 2.2 and later (40 days) to 77.1 +/- 3.0 mmHg. Meanwhile, aestivation had no effect on pHa and hematocrit. The blood pressures were equal for animals in the water or in the burrow (P(mean) similar to 30 mmHg), and cardiac frequency (f(H)) fell from 31 beats min(-1) to 22 beats min(-1) during 40 days of aestivation. The osmolality (mOsm kg H(2)O(-1)) was elevated after 20 and 40 days of aestivation but declined upon return to water. The transition front activity to aestivation involves new set-points for the variables that determine the acid-base status and PaO(2) of the animals, along with a reduction of cardiac frequency. (C) 2008 Elsevier B.V. All rights reserved.

Thermostable variants of the recombinant xylanase A from Bacillus subtilis produced by directed evolution show reduced heat capacity changes

Directed evolution techniques have been used to improve the thermal stability of the xylanase A from Bacillus subtilis (XylA). Two generations of random mutant libraries generated by error prone PCR coupled with a single generation of DNA shuffling produced a series of mutant proteins with increasing thermostability. The most Thermostable XylA variant from the third generation contained four mutations Q7H, G13R, S22P, and S179C that showed an increase in melting temperature of 20 degrees C. The thermodynamic properties Of a representative subset of nine XylA variants showing a range of thermostabilities were measured by thermal denaturation as monitored by the change in the far ultraviolet circular dichroism signal. Analysis of the data from these thermostable variants demonstrated a correlation between the decrease in the heat capacity change (Delta C(p)) with an increase in the midpoint of the transition temperature (T(m)) on transition from the native to the unfolded state. This result could not be interpreted within the context of the changes in accessible surface area of the protein on transition from the native to unfolded states. Since all the mutations are located at the surface of the protein, these results suggest that an explanation of the decrease in Delta C(p) on should include effects arising from the prot inlsolvent interface.