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.

OCT findings in macular hole formation in eyes with complete vitreofoveal separation

The current study describes the morphologic macular features in two eyes that developed full-thickness macular holes in the setting of documented vitreofoveal separation. Using third-generation optical coherence tomography, complete vitreofoveal separation associated with the disruption of the inner foveal retina was documented in both cases. Five months after presentation, decreased vision and epiretinal membrane formation associated with development of a full-thickness macular hole were observed in the first patient. In the second patient, a full-thickness macular hole was demonstrated by optical coherence tomography 6 weeks after presentation. These findings suggest that full-thickness macular holes may develop in eyes with vitreofoveal separation. Evidence of the disturbance of the inner foveal architecture on optical coherence tomography indicates the potential role of factors other than anteroposterior or oblique vitreoretinal tractional forces in the genesis of some full-thickness macular holes.

Brazilian Version of the Addenbrooke Cognitive Examination-revised in the Diagnosis of Mild Alzheimer Disease

Objective: To investigate the accuracy of the Brazilian version of the Addenbrooke Cognitive Examination-revised (ACE-R) in the diagnosis of mild Alzheimer disease (AD). Background: The ACE-R is an accurate and brief cognitive battery for the detection of mild dementia, especially for the discrimination between AD and frontotemporal dementia. Methods: The battery was administered to 31 patients with mild AD and 62 age-matched and education-matched cognitively healthy controls. Both groups were selected using the Dementia Rating Scale and were submitted to the ACE-R. Depression was ruled out in both groups by the Cornell Scale for Depression in Dementia. The performance of patients and controls in the ACE-R was compared and receiver operator characteristic curve analysis was undertaken to ascertain the accuracy of the instrument for the diagnosis of mild AD. Results: The mean scores at the ACE-R were 63.10 +/- 10.22 points for patients with AD and 83.63 +/- 7.90 points for controls. The cut-off score < 78 yielded high diagnostic accuracy (receiver operator characteristic area under the curve = 0.947), with 100% sensitivity, 82.26% specificity, 73.8% positive predictive value, and 100% negative predictive value. Conclusions: The Brazilian version of the ACE-R displayed high diagnostic accuracy for the identification of mild AD in the studied sample.

Protective effect of Calendula officinalis extract against UVB-induced oxidative stress in skin: Evaluation of reduced glutathione levels and matrix metalloproteinase secretion

Background and purpose: Calendula officinalis flowers have long been employed time in folk therapy, and more than 35 properties have been attributed to decoctions and tinctures from the flowers. The main uses are as remedies for burns (including sunburns), bruises and cutaneous and internal inflammatory diseases of several origins. The recommended doses are a function both of the type and severity of the condition to be treated and the individual condition of each patient. Therefore, the present study investigated the potential use of Calendula officinalis extract to prevent UV irradiation-induced oxidative stress in skin. Methods: Firstly, the physico-chemical composition of marigold extract(ME) (hydroalcoholic extract)was assessed and the in vitro antioxidant efficacy was determined using different methodologies. Secondly, the cytotoxicity was evaluated in L929 and HepG2 cells with the MTT assay. Finally, the in vivo protective effect of ME against UVB-induced oxidative stress in the skin of hairless mice was evaluated by determining reduced glutathione (GSH) levels and monitoring the secretion/activity of metalloproteinases. Results and conclusions: The polyphenol, flavonoid, rutin and narcissin contents found in ME were 28.6 mg/g, 18.8 mg/g, 1.6 mg/g and 12.2 mg/g, respectively and evaluation of the in vitro antioxidant activity demonstrated a dose-dependent effect of ME against different radicals. Cytoxicity experiments demonstrated that ME was not cytotoxic for L929 and HepG2 cells at concentrations less than or equal to of 15 mg/mL However, concentrations greater than or equal to 30 mg/mL, toxic effects were observed. Finally, oral treatment of hairless mice with 150 and 300 mg/kg of ME maintained GSH levels close to non-irradiated control mice. In addition, this extract affects the activity/secretion of matrix metalloproteinases 2 and 9 (MMP-2 and -9) stimulated by exposure to UVB irradiation. However, additional studies are required to have a complete understanding of the protective effects of ME for skin. (C) 2009 Elsevier Ireland Ltd. All rights reserved.

Sexual Dysfunction Treatment in a Patient With Mullerian Agenesy Submitted to Neovaginoplasty: A Case Report

Vagina agenesis is a rare entity. Mayer-Rokitansky-Kuster-Hauser syndrome is the most significant cause of vagina agenesis, whereas the second most common cause is complete androgen syndrome. Surgical treatment can propitiate a vaginal reconstruction, but sexual function depends on several factors that affect sexual performance. Many reports focus on the intraoperative and postoperative results and only describe the global approach to these patients, but reports focusing on the management of these patients to enable them to have a normal sexual life are lacking. This case report highlights a multidisciplinary treatment for this kind of morbidity and emphasizes the necessity of incorporating careful attention to sexual health in the treatment of these patients so that they may achieve a good therapeutic response, resulting in a pleasurable sexual life and a good quality of living.

Novel Pathogenic Mutations and Copy Number Variations in the VPS13A Gene in Patients With Chorea-Acanthocytosis

Chorea-acanthocytosis (ChAc) is a rare autosomal recessive neurodegenerative disorder caused by loss of function mutations in the vacuolar protein sorting 13 homolog A (VPS13A) gene that encodes chorein. It is characterized by adult-onset chorea, peripheral acanthocytes, and neuropsychiatric symptoms. In the present study, we performed a comprehensive mutation screen, including sequencing and copy number variation (CNV) analysis, of the VPS13A gene in ChAc patients. All 73 exons and flanking regions of VPS13A were sequenced in 35 patients diagnosed with ChAc. To detect CNVs, we also performed real-time quantitative PCR and long-range PCR analyses for the VPS13A gene on patients in whom only a single heterozygous mutation was detected. We identified 36 pathogenic mutations, 20 of which were previously unreported, including two novel CNVs. In addition, we investigated the expression of chorein in 16 patients by Western blotting of erythrocyte ghosts. This demonstrated the complete absence of chorein in patients with pathogenic mutations. This comprehensive screen provides an accurate and useful method for the molecular diagnosis of ChAc. (C) 2011 Wiley-Liss, Inc.

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.

Influence of aging, tidal volume, and respiratory rate on Doppler echocardiographic indices of diastolic function in normal male subjects: A quantitative evaluation

Background: Although the influence of respiration on ventricular filling, as evaluated by Doppler technique, and the evaluation of diastolic velocities of mitral valve annulus (MVA), as measured by Doppler tissue imaging (DTI), can provide valuable information for the study of left ventricular (LV) diastolic function, the concomitant effects of aging, tidal volume (TV), and respiratory rate (RR) on these velocities have not been quantitatively investigated. Methods: We evaluated 12 normal male volunteers (Group I) aged 20-26 years (mean: 22.8) and 8 normal subjects aged 41 to 54 years old (mean: 45.9) (Group II). Using DTI we measured peak early (E-a) and late (A(a)) velocities of longitudinal axis expansion at lateral and medial MVA. Doppler mitral and tricuspid flow velocities were measured: peak early (E) and late (A) inflow velocity, early (E-i) and late (A(i)) flow integral, and deceleration time of peak early mitral flow velocity (DT). Respiratory cycles were simultaneously recorded at RR of 9, 12, 15, and 18 cycles/min and TV of 600 and 900 mL during respiration (RESP). Results and conclusions: (1) E, A, and A(i) in MV had negligible change during respiration, but E-i was significantly reduced during inspiration; (2) DT reduced slightly with inspiration, but the change was significant only with TV of 900 mL; (3) an important increase of E in right ventricular flow was observed during inspiration; (4) variations of RR and TV did not significantly influence right and left ventricular inflow in normal subjects, in the conditions of this investigation; (5) a significant increase of E-a at medial MVA was documented during inspiration only in young subjects; (6) a significant decrease of A(a) at medial MVA was observed during inspiration in both groups of volunteers; (7) RR and TV did not influence MVA velocities in young and adult subjects; (8) a consistent reduction in E-a and a significant increase in A(a) were observed with increasing age; (9) these changes were more conspicuous and consistent than those documented in ventricular filling when young and middle-age men are compared, suggesting that the DTI is more sensitive to detect changes in diastolic function; and (10) in addition, these data suggest that, for evaluation of diastolic function, in clinical context, it is not necessary to control rigorously RR or TV.

The Impact of Preexisting Myocardial Remodeling on Ventricular Function Early after Tetralogy of Fallot Repair

Background: Twenty-three patients (median age 23 months) who underwent Fallot`s tetralogy repair were investigated prospectively to detect a possible association between histopathologic myocardial remodeling and echocardiographic findings of systolic or diastolic ventricular dysfunction. Methods: Intraoperatively resected infundibular bands and subendocardial biopsy samples from the right ventricle (RV) and left ventricle were obtained for histopathologic evaluation. Tissue Doppler echocardiographic interrogation of the ventricles was performed before surgery and in the postoperative period. Results: Histopathologic data revealed hypertrophy of the RV cardiomyocytes and increased interstitial collagen in both ventricles. Mean values of RV isovolumic acceleration decreased significantly at the third evaluation compared with the preoperative values (P = .006). RV myocardial fibrosis greater than 8.3% was associated with a probability of altered E` of at least 0.7 (odds ratio = 2.31). Conclusion: Preoperative histologic myocardial remodeling influenced the postoperative RV function in this group of patients with late repair. Further studies are necessary to evaluate the myocardium in younger patients and to define its influence in the long-term follow-up. (J Am Soc Echocardiogr 2010;23:912-8.)

Chronic alcoholism associated with diabetes impairs erectile function in rats

OBJECTIVE To investigate the effects of chronic ethanol consumption and diabetes on nitric oxide (NO)-mediated relaxation of cavernosal smooth muscle (CSM). MATERIAL AND METHODS Male Wistar rats were divided into four groups: control, isocaloric, diabetic and ethanol-diabetic. The CSMs were mounted in organ chambers for measurement of isometric tension. Contraction of the strips was induced by electrical field stimulation (EFS, 1-32 Hz) and phenylephrine. We also evaluated the effect of ethanol consumption on the relaxation induced by acetylcholine (ACh; 0.01-1000 mu mol/L), sodium nitroprusside (SNP, 0.01-1000 mu mol/L) or EFS (1-32 Hz) in strips pre-contracted with phenylephrine (10 mu mol/L). Immunoexpression of endothelial NO synthase (eNOS) and inducible NOS (iNOS) was also accessed. RESULTS The endothelium-dependent relaxation induced by ACh was decreased in CSM from ethanol-diabetic rats when compared with the controls, with a mean (sem) of 21 (4) vs 37 (2)%. Similarly, the potency and maximal responses induced by SNP were reduced in the ethanol-diabetic [3.97 (0.38) and 85 (1)%, respectively] and diabetic groups [3.78 (0.56) and 81 (2)%, respectively] when compared with the controls [5.3 (0.22) and 90 (3)%, respectively] and isocaloric [5.3 (0.19) and 92 (1)%, respectively] groups. Noradrenergic nerve-mediated contractions of CSM in response to EFS were increased in rats from ethanol-diabetic and diabetic groups when compared with the control and isocaloric groups. Conversely, there were no differences in EFS-induced relaxation among the groups. The immunostaining assays showed overexpression of eNOS and iNOS in the CSM from diabetic and ethanol-diabetic rats when compared with the control and isocaloric rats. CONCLUSION There was an impairment of relaxation of CSM from ethanol-diabetic and diabetic rats that involved a decrease in the NO-cyclic guanosine monophosphate signalling pathway by endothelium-dependent mechanisms accompanied by a change in the CSM contractile sensitivity.

Effects of Nicotine Exposure on Renal Function of Normal and Hypercholesterolemic Rats

Background/Aims: Renal risks of nicotine exposure associated with hypercholesterolemia are still unknown. Methods: Thus, hypercholesterolemic rats (HC) and their control (C) were evaluated by inulin clearance (InCl) measured at baseline and during nicotine infusion (100 mu g/kg b.w.). Five groups were studied: (i) C; (ii) DEN (C submitted to a renal denervation); (iii) C + L-arginine (0.25% in drinking water); (iv) HC, and (v) HC + L-arginine (0.25% in drinking water). Furthermore, C and HC had their renal blood flow (RBF) measured and they have also been chronically treated with nicotine (12.5 mu g/ml in drinking water) to assess InCl on the 8th day. Results: Nicotine increased blood pressure in C, DEN and HC and reduced InCl only in C. L-Arginine treatment blunted nicotine effects on blood pressure and increased InCl only in C. Moreover, nicotine did not change RBF in C but elicited in HC, whereas renal vascular resistance was increased in C and unchanged in HC. Indeed, chronic nicotine exposure has also reduced InCl in C. Conclusion: Nicotine acted on the adrenergic system and nitric oxide counteracted this action in C, but the same may not be applied to HC. An impairment in renal autoregulation may explain why InCl was unchanged in HC. Copyright (C) 2009 S. Karger AG, Basel

The use of MPB70-ELISA for the diagnosis of caprine tuberculosis in Brazil

After one clinical case that evidenced the outbreak, a complete screening by intradermal tuberculin test was performed in one goat herd in Brazil. The herd was composed by 500 animals and 83 of them (16.6%) showed to be reactive to the comparative double cervical intradermal test. Four months after the test, all the 83 reactive animals were slaughtered and blood samples were collected from 45 of them, for serological assays. From those 45, 32 were randomly chosen for necropsy and histopathological and bacteriological procedures were conducted. Histopathology evidenced at least one characteristic lesion of tuberculosis in each animal, with typical granulommas where acid-fast bacilli (AFB) could be observed. Bacteriology was positive for Mycobacterium bovis in 22 samples (68.7%), therefore confirming the etiology of the outbreak. Sera of 45 animals plus 20 other from a certified free tuberculosis farm were tested in an ELISA using the recombinant M.bovis protein MPB70 as capture antigens. From those, 43 were reactive to the test, with high ODs results, considering a cut-off point established by ROC curve analyzing results (cut-off = 0.8; mean = 0.55; range: 0.157-1.357). These results suggest that MPB70-ELISA can be considered as a reliable tool to diagnose tuberculosis in goat herds, since this assay was capable to correctly detect 95.6% of the animals here examined.

Renormalizing the kinetic energy operator in elementary quantum mechanics

In this paper, we consider solutions to the three-dimensional Schrodinger equation of the form psi(r) = u(r)/r, where u(0) not equal 0. The expectation value of the kinetic energy operator for such wavefunctions diverges. We show that it is possible to introduce a potential energy with an expectation value that also diverges, exactly cancelling the kinetic energy divergence. This renormalization procedure produces a self-adjoint Hamiltonian. We solve some problems with this new Hamiltonian to illustrate its usefulness.

Complete genome analysis of a rabies virus isolate from Brazilian wild fox

The complete genome sequence of wild-type rabies virus (RABV) isolated from a wild Brazilian hoary fox (Dusicyon sp.), the BR-Pfx1 isolate, was determined and compared with fixed RABV strains. The genome structure and organization of the BR-Pfx1 isolate were composed of 11,924 nt and included the five standard genes of rhabdoviruses. Sequences of mRNA start and stop signals for transcription were highly conserved among all structural protein genes of the BR-Pfx1 isolate. All amino acid residues in the glycoprotein (G) gene associated with pathogenicity were retained in the BR-Pfx1 isolate, while unique amino acid substitutions were found in antigenic region I of the nucleoprotein gene and III of G. These results suggest that although the standard genome structure and organization of the RABV isolate are common between the BR-Pfx1 isolate and fixed RABV strains, the unique amino acid substitutions in functional sites of the BR-Pfx1 isolate may result in different biological characteristics from fixed RABV strains.

Ovarian function in Nelore (Bos taurus indicus) cows after post-ovulation hormonal treatments

Maternal recognition of pregnancy in the cow requires successful signaling by the conceptus to block luteolysis. Conceptus Growth and function depend on an optimal uterine environment, regulated by luteal progesterone. The objective of this study was to test strategies to optimize luteal function, as well as prevent a dominant follicle from initiating luteolysis. Nelore (Bos taurus indicus) beef cows (n = 40) were submitted to a GnRH/PGF(2 alpha)/GnRH protocol. Cows that ovulated from a dominant ovarian follicle (ovulation = Day 0) were allocated to receive: no additional treatment (Gc; n = 7); 3000 IU of hCG on Day 5 (G(hCG); n = 5); 5 mg of estradiol-17 beta on Day 12 (G(E2); n = 6); or 3000 IU of hCG on Day 5 and 5 mg of estradiol-17 beta on Day 12 (G(hCG/E2); n = 5). Ultrasonographic imaging of the ovaries, assessment of plasma progesterone concentration, and detection of estrus were done daily from Day 5 to the day of subsequent ovulation. Treatment with hCG induced an accessory CL, increased CL volume, and plasma progesterone concentration throughout the luteal phase (P < 0.01). Estradiol-17 beta induced atresia and recruitment of a new wave of follicular growth; it eliminated a potentially estrogen-active, growing ovarian follicle within the critical period for maternal recognition of pregnancy, but it also hastened luteolysis (Days 16 or 17 vs. Days 18 or 19 in non-treated cows). In conclusion, the approaches tested enhanced luteal function (hCG) and altered ovarian follicular dynamics (estradiol-17 beta), but were unable to extend the life-span of the CL in Nelore cows. (c) 2008 Elsevier Inc. All rights reserved.