Equal Numbers of Neuronal and Nonneuronal Cells Make the Human Brain an Isometrically Scaled-Up Primate Brain

The human brain is often considered to be the most cognitively capable among mammalian brains and to be much larger than expected for a mammal of our body size. Although the number of neurons is generally assumed to be a determinant of computational power, and despite the widespread quotes that the human brain contains 100 billion neurons and ten times more glial cells, the absolute number of neurons and glial cells in the human brain remains unknown. Here we determine these numbers by using the isotropic fractionator and compare them with the expected values for a human-sized primate. We find that the adult male human brain contains on average 86.1 +/- 8.1 billion NeuN-positive cells (""neurons"") and 84.6 +/- 9.8 billion NeuN-negative (""nonneuronal"") cells. With only 19% of all neurons located in the cerebral cortex, greater cortical size (representing 82% of total brain mass) in humans compared with other primates does not reflect an increased relative number of cortical neurons. The ratios between glial cells and neurons in the human brain structures are similar to those found in other primates, and their numbers of cells match those expected for a primate of human proportions. These findings challenge the common view that humans stand out from other primates in their brain composition and indicate that, with regard to numbers of neuronal and nonneuronal cells, the human brain is an isometrically scaled-up primate brain. J. Comp. Neurol. 513:532-541, 2009. (c) 2009 Wiley-Liss, Inc.

Preliminary findings from a new animal model for Peyronie`s disease involving extracorporeal shock waves

To develop an experimental model in rabbits to analyse the efficiency of extracorporeal shock wave therapy (ESWT) for Peyronie`s disease. We used 15 adult male rabbits divided into three equal groups. In group 1 (no penile ESWT) rabbits had three sessions of ESWT with 2000 shocks each (15 kV), but a rubber mat was placed between the shock head and rabbit to protect the penis; the rabbits were killed at 7 days after the last session of ESWT. In group 2 the rabbits had three sessions of ESWT using the same parameters, and were killed immediately after the last session to analyse the penis. In group 3 the rabbits had three sessions of ESWT as before but were killed at 7 days after the last session, and the penile tissue analysed macroscopically and histologically. The results showed clearly that the model was efficient, creating a similar situation to that when applying ESWT in the human penis. All of the rabbits in groups 2 and 3 had haematomas and diffuse petechiae after ESWT, and only four had urethral and penile bleeding. Almost all macroscopic changes disappeared after 48 h and only one rabbit in group 3 after 7 days had a haematoma on the dorsal penile surface. The histology (assessed using haematoxylin and eosin staining) of the cavernous body of the penis showed: unchanged histology in group 1; in group 2 there was a dilated and congested vascular space in the cavernous body, with interstitial extensive bleeding in the dermis; and in group 3 there was an increase in interstitial fibrous tissue in the cavernous septum, with deposition of collagen fibres and thickening of the tunica albuginea. The present model was efficient in producing tissue injury in the normal penis when treated with ESWT, suggesting that this promising model should be considered for use future studies of Peyronie`s disease.

UPGRADING THE GLEASON SCORE IN EXTENDED PROSTATE BIOPSY: IMPLICATIONS FOR TREATMENT CHOICE

Purpose: To determine the incidence of overestimation of Gleason score (GS) in extended prostate biopsy, and consequently circumventing unnecessary aggressive treatment. Methods and Materials: This is a retrospective study of 464 patients who underwent prostate biopsy and radical prostatectomy between January 2001 and November 2007. The GS from biopsy and radical prostatectomy were compared. The incidence of overestimation of GS in biopsies and tumor volume were studied. Multivariate analysis was applied to find parameters that predict upgrading the GS in prostate biopsy. Results: The exact agreement of GS between prostate biopsy and radical prostatectomy occurred in 56.9% of cases. In 29.1% cases it was underestimated, and it was overestimated in 14%. One hundred and six (22.8%) patients received a diagnosis of high GS (8, 9, or 10) in a prostate biopsy. In 29.2% of cases, the definitive Gleason Score was 7 or lower. In cases in which GS was overestimated in the biopsy, tumors were significantly smaller. In multivariate analysis, the total percentage of tumor was the only independent factor in overestimation of GS. Tumors occupying less than 33% of cores had a 5.6-fold greater chance of being overestimated. Conclusion: In the extended biopsy era and after the International Society of Urological Pathology consensus on G, almost one third of tumors considered to have high GS at the biopsy may be intermediate-risk cancers. In that condition, tumors are smaller in biopsy. This should be remembered by professionals involved with prostate cancer to avoid overtreatment and undesirable side effects. (c) 2009 Elsevier Inc.

Polymerase chain reaction compared to other laboratory findings and to clinical evaluation in the diagnosis of cutaneous tuberculosis and atypical mycobacteria skin infection

Cutaneous tuberculosis has re-emerged in the last 15 years together with the higher incidence of pulmonary tuberculosis and multidrug resistance. The choice for a single diagnostic tool among the many available today is a challenge. Our objective was to compare polymerase chain reaction (PCR) with other exams in the diagnosis of cutaneous tuberculosis and atypical mycobacteria skin infection. PCR and a set of five different exams were performed in 32 patients (34 samples of paraffin-embedded tissue) evaluated for 3 years in a university hospital, considering the response to mycobacterial infection treatment as a positive case. PCR was the most sensitive (88%) and specific (83%) exam. Culture, immunohistochemistry and acid-fast bacilli were not in agreement with clinical response to treatment. Although PCR is a useful tool, careful clinical exam is still the gold standard for the evaluation and treatment of cutaneous tuberculosis and mycobacteria skin infection.

Esophageal CandidiasisAn Adverse Effect of Inhaled Corticosteroids Therapy

Over the last few decades, inhaled corticosteroids (ICs) became the cornerstone in the treatment of persistent asthma. Their use improved asthma control, decreased mortality and also minimized adverse reactions associated with systemic steroid. Esophageal candidiasis is a rare complication resulting from the use of ICs. Although, in recent years, as their prescriptions has increased, more cases have been reported, especially in Japan. Listed are 4 case reports regarding esophageal candidiasis in asthmatic patients associated with inhaled budesonide administration. In the cases reported herein, the use of a different device of dry powder budesonide might have favored esophageal drug deposition and Candida infection. Patients denied using systemic corticosteroids in the previous 6 months. Furthermore, none of the patients presented Diabetes mellitus, malignant disease, HIV infection, or other immunosuppressive conditions. We conclude that patients treated with high doses of ICs are at higher risk of developing esophageal candidiasis. These patients should undergo upper gastrointestinal endoscopy whenever they present symptoms. Nevertheless, we must keep in mind that infection might also be asymptomatic and esophageal candidiasis prevalence may be higher than that reported thus far.

Determination of trace elements in human brain tissues using neutron activation analysis

Neutron activation analysis was applied to assess trace element concentrations in brain tissues from normal (n = 21) and demented individuals (n = 21) of both genders aged more than 50 years. Concentrations of the elements Br, Fe, K, Na, Rb, Se and Zn were determined. Comparisons were made between the results obtained for the hippocampus and frontal cortex tissues, as well as, those obtained in brains of normal and demented individuals. Certified reference materials, NIST 1566b Oyster Tissue and NIST 1577b Bovine Liver were analyzed for quality of the analytical results.

Penile erection induced in vivo by a purified toxin from the Brazilian spider Phoneutria nigriventer

OBJECTIVES To verify the effect on erectile tissue of mice of two neuropeptides extracted from the poison of a spider, Phoneutric nigriventer, (Tx2-5 and -6. termed `eretina`) after direct injection into the corpus cavernosum, to assess the minimum dosage necessary for effect. the time for initiation of action, the local duration of the erection, histological effects and the presence of local and systemic side-effects. MATERIALS AND METHODS When applied intraperitoneally, eretina promotes the relaxation of cavernous smooth muscle, thus causing penile erection. Thirty-five mice were divided in two groups; 10 control mice were injected 20 mu L of saline solution, and in the treated group, 25 mice were divided into groups of five and each subgroup received eretina in decreasing doses (0.024, 0.012, 0.006, 0.003 and 0.0015 mu g/kg) until the minimum dose that produced an erection was determined. After treatment 211 mice were monitored to determine the response and any collateral effects. RESULTS The minimum dose producing an erection was 0.006 mu g/kg, the five mice in this group having evidence of an erection at 35-45 min after injection. The histology of the cavernosum of mice treated with eretina showed dilatation and congestion of the vascular spaces with more blood than in controls. With the minimum dose there were no local or systemic collateral effects and the erection was lost after 120-140 min. CONCLUSION The minimum dose of eretina producing an erection in mice was determined. and the agent was safe for this use as it did not produce any collateral toxic effects. These studies indicate a possible means of determining the mechanism of action of eretina.

Cdx2, cytokeratin 20, thyroid transcription factor 1, and prostate-specific antigen expression in unusual subtypes of prostate cancer

There are some unusual histologic variants of prostate carcinoma, including mucinous, signet-ring cells, and ductal carcinomas that can metastasize in a problematic way and simulate lung, colorectal, or bladder primaries. Currently, antibodies that are organ-specific have been used in the routine surgical pathology practice. Our aim is to study the profile of expression of Cdx2, thyroid transcription factor 1 (TTF1), and cytokeratin 20 (CK20) in prostate cancer with unusual histologic finding. Twenty-nine prostate adenocarcinomas with unusual histologic findings were submitted to immunohistochemistry with prostate-specific antigen (PSA), CK20, Cdx2, and TTF1 antibodies. There were 7 mucinous, 5 ductal, 2 signet-ring cells, and 15 usual acinar adenocarcinomas with focal mucinous differentiation. To compare the results with usual acinar adenocarcinomas, we studied 10 primary and their respective lymph node metastases in a tissue microarray, 2 unusual metastatic adenocarcinomas, and 6 usual acinar high-grade carcinomas. For tumors with special histologic finding, Cdx2 was expressed by 9 (31.0%) mucinous, signet-cell, or with focal mucinous differentiation. Thyroid transcription factor I was moderately positive in mucinous differentiation areas of 2 (6.9%) adenocarcinomas. Cytokeratin 20 was expressed by 9 (31.0%) tumors, among them, 3 ductal adenocarcinomas. Prostate-specific antigen was positive in 28 (96.6%) cases and negative in I ductal adenocarcinoma. There was only I worrisome ductal adenocarcinoma that was strongly CK20 positive and PSA negative. Almost one third of mucinous prostate carcinomas express Cdx2. Cytokeratin 20 can be positive also in one third of prostate carcinomas, especially the ductal type. Pathologist should be alert when evaluating immumohistochemical profiles of unusual histologic findings of prostate cancer, mostly in distant sites. (C) 2008 Elsevier Inc. All rights reserved.

Polymorphisms of the matrix metalloproteinases associated with prostate cancer

Prostate cancer (PCa) is the most common type of malignant tumor in Brazilian males. Single nucleotide polymorphisms (SNPs) have been demonstrated to be present in the promoter region of matrix metalloproteinase (MMP) genes and have been associated with the development and progression of some cancers. In this study, our aim was to investigate the association between the polymorphisms of MMP1, 2, 7, and 9 and susceptibility, and their correlation with the classic prognostic parameters of PCa. For genes MMP1, 2 and 9, the frequencies of the polymorphic homozygote genotypes were higher in the control group than in the PCa group (P<0.0001). We conclude that the MMP1, 2 and 9 polymorphisms are more common in the control group than in patients with PCa, and may have a protective effect in the development of this neoplasia.

The effect of the number of biopsy cores on the concordance between prostate biopsy and prostatectomy Gleason score - A prostate volume-controlled study

Context.-Studies analyzing the concordance of biopsy and radical prostatectomy (RP) Gleason scores have limitations. Some included 2 or more centers, used historical controls from the early prostate specific antigen era or lacked a clear definition of the biopsy schemes. Furthermore, most did not control the results for prostate volume. Objective.-To confirm whether prediction of RP Gleason score can be optimized by taking more biopsy cores in a contemporary series of patients, with pathologic samples analyzed by the same pathologist, and controlling these results for prostate volume. Design.-The study comprised a retrospective case-control analysis of 393 patients with prostate cancer treated with RP. Patients were divided into 3 groups: those in group 1 underwent a 6-core biopsy; group 2, an 8-core biopsy; and group 3, a 10 or more-core biopsy. Concordance rates between biopsy and RP Gleason scores, as well as the rates of undergrading and overgrading, were determined for each biopsy scheme. Results.-Concordance rates were 60.9%, 58.3%, and 64.6% for patients from groups 1, 2, and 3, respectively (P = .18). When we analyzed patients with prostate volumes of less than 50 cm(3), concordance rates were 58.3%, 58.3%, and 65.1% for each group, respectively (P = .03). Among patients with prostate volumes of 50 cm3 or more, concordance rates were 70%, 58.1%, and 63.6%, respectively (P = .66). Conclusions.-Taking 10 or more cores can improve the prediction of RP Gleason score in patients with prostate volumes of less than 50 cm3. For patients with prostate volumes of 50 cm3 or more, increasing the biopsy cores to 10 or more did not improve prediction of RP Gleason score.

Association of a homozygous nonsense caveolin-1 mutation with Berardinelli-Seip congenital lipodystrophy

Context: Berardinelli-Seip congenital lipodystrophy (BSCL) is a rare recessive disease characterized by near absence of adipose tissue, resulting in severe dyslipidemia and insulin resistance. In most reported cases, BSCL is due to alterations in either seipin, of unknown function, or 1-acylglycerol-3- phosphate acyltransferase-beta (AGPAT2), which catalyzes the formation of phosphatidic acid. Objective: We sought to determine the genetic origin of the unexplained cases of BSCL. We thus sequenced CAV1, encoding caveolin-1, as a candidate gene involved in insulin signaling and lipid homeostasis. CAV1 is a key structural component of plasma membrane caveolae, and Cav1-deficient mice display progressive loss of adipose tissue and insulin resistance. Design: We undertook phenotyping studies and molecular screening of CAV1 in four patients with BSCL with no mutation in the genes encoding either seipin or AGPAT2. Results: A homozygous nonsense mutation (p.Glu38X) was identified in CAV1 in a patient with BSCL born from a consanguineous union. This mutation affects both the alpha-and beta-CAV1 isoforms and ablates CAV1 expression in skin fibroblasts. Detailed magnetic resonance imaging of the proband confirmed near total absence of both sc and visceral adipose tissue, with only vestigial amounts in the dorsal sc regions. In keeping with the lack of adipose tissue, the proband was also severely insulin resistant and dyslipidemic. In addition, the proband had mild hypocalcemia likely due to vitamin D resistance. Conclusions: These findings identify CAV1 as a new BSCL-related gene and support a critical role for caveolins in human adipocyte function.

Change in expression of miR-let7c, miR-100, and miR-218 from high grade localized prostate cancer to metastasis

Objective: MicroRNAs (miRNAs) are small noncoding regulatory RNAs (19-25 nucleotides) that play a major role in regulation of gene expression. They are responsible for the control of fundamental cellular processes that has been reported to be involved in human tumorigenesis. The characterization of miRNA profiles in human tumors is crucial for the understanding of carcinogenesis processes, finding of new tumor markers, and discovering of specific targets for the development of innovative therapies. The aim of this study is to find miRNAs involved in prostate cancer progression comparing the profile of miRNA expressed by localized high grade carcinoma and bone metastasis. Material and methods: Two groups of tumors where submitted to analyses. The first is characterized by 18 patients who underwent radical prostatectomy for treatment of localized high grade prostate carcinoma (PC) with mean Gleason score 8.6, all staged pT3. The second group is composed of 4 patients with metastatic, androgen-independent prostate carcinoma, and 2 PC cell lines. LNCaP derived from a metastatic PC to a lymph node, and another derived from an obstructive, androgen-independent PC (PcBRA1). Expression analysis of 14 miRNAs was carried out using quantitative RT-PCR. Results: miR-let7c, miR-100, and miR-218 were significantly overexpressed by all localized high GS, pT3 PC in comparison with metastatic carcinoma. (35.065 vs. 0.996 P < 0.001), (55.550 vs. 8.314, P = 0.010), and (33.549 vs. 2.748, P = 0.001), respectively. Conclusion: We hypothesize that miR-let7c, miR-100, and miR-218 may be involved in the process of metastasization of PC, and their role as controllers of the expression of RAS, c-myc, Laminin 5 beta 3, THAP2, SMARCA5, and BAZ2A should be matter of additional studies. (C) 2011 Elsevier Inc. All rights reserved.

Enhancement of diagnostic efficiency by a gamma interferon release assay for pulmonary tuberculosis

This study was designed to examine the use of the QuantiFERON-TB Gold assay as an aid in the diagnosis of active pulmonary tuberculosis (TB) in Brazilian patients. Using the receiver operating characteristic curve, the cutoff was adjusted to >= 0.20 IU/ml. The sensitivity increased to 86%, with 100% specificity. All TB patients with negative sputum smear microscopy and negative culture results were positive using this test.

Genotype and mating type distribution within clinical Cryptococcus neoformans and Cryptococcus gattii isolates from patients with cryptococcal meningitis in Uberaba, Minas Gerais, Brazil

We molecularly characterized 81 cryptococcal isolates recovered from cerebrospinal fluid samples of 77 patients diagnosed between 1998 and 2007 as having cryptococcal meningitis in Uberaba Minas Gerais, Brazil. Fifty-seven (74%) were male with a mean age 35.6 years. Seventy-two (88.9%) of the isolates were from 68 AIDS patients and cryptococcosis was the first AIDS-defining condition in 38 (55.9%) patients. Cryptococcosis and AIDS were simultaneously diagnosed in 25 (65.8%) of these 38 patients. Genotypes were characterized through the use of URA5 restriction fragment length polymorphisms analysis, the genetic variability was determined using PCR-fingerprinting with the minisatellite-specific primer M13, and the mating type and serotypes were established by PCR. Seventy-six of the 81 isolates were Cryptococcus neoformans (93.8%), while the remaining five were C. gattii (6.1%), but all were mating type a. C. neoformans isolates were genotype VNI (serotype A), while C. gattii isolates were VGII. Four of the latter isolates were identical, but only two were from AIDS patients. Six of the nine isolates from non-AIDS patients were VNI. PCR fingerprints of the isolates from two of the three AIDS patients with clinical relapse were 100% identical. The predominance of VNI and mating type a is in accordance with data from other parts of the world. The occurrence of VGII in Minas Gerais indicates a geographical expansion within Brazil.

In vitro antifungal drug susceptibilities of dermatophytes microconidia and arthroconidia

Objectives: Arthroconidia have been considered as the primary cause of infection by dermatophytes. However, the in vitro antifungal testing evaluates the responses mainly of microconidia or hyphae, and dermatophytes in vivo often produce arthroconidia, a cellular structure presumably more resistant to antifungals. The aim of this study was to compare the in vitro susceptibility of microconidia and arthroconidia of Trichophyton rubrum, Trichophyton tonsurans and Trichophyton equinum to griseofulvin, itraconazole, terbinafine, fluconazole, amphotericin B and hygromycin B. Methods: Microconidia and arthroconidia were produced in vitro, and their susceptibility to each drug was evaluated by assessing the CLSI M38-A broth microdilution method. Results: Arthroconidia of all strains analysed appeared to be more resistant to fluconazole, griseofulvin and itraconazole than microconidia. The MIC of terbinafine was the same for microconidia and arthroconidia for all strains, and the MIC of amphotericin B for microconidia and arthroconidia was the same for isolates of T. equinum and T. tonsurans, but differed for T. rubrum. Finally, the level of resistance of microconidia for all strains towards the antibiotic hygromycin B was from 25 to 400 mg/L. Conclusions: The difference in the susceptibility between microconidia and arthroconidia depends on the drug and on the strain, and may be one of the causes of therapeutic failure. Also, the level of resistance to the antibiotic hygromycin B presented by microconidia of these isolates will allow the use of hygromycin resistance as a dominant marker in fungal transformation procedures in future studies of gene function.