Neuroproteomics: Unveiling the Molecular Insights of Psychiatric Disorders with a Focus on Anxiety Disorder and Depression.

Anxiety and depression are two of the most common mental disorders worldwide, with a lifetime prevalence of up to 30%. These disorders are complex and have a variety of overlapping factors, including genetic, environmental, and behavioral factors. Current pharmacological treatments for anxiety and depression are not perfect. Many patients do not respond to treatment, and those who do often experience side effects. Animal models are crucial for understanding the complex pathophysiology of both disorders. These models have been used to identify potential targets for new treatments, and they have also been used to study the effects of environmental factors on these disorders. Recent proteomic methods and technologies are providing new insights into the molecular mechanisms of anxiety disorder and depression. These methods have been used to identify proteins that are altered in these disorders, and they have also been used to study the effects of pharmacological treatments on protein expression. Together, behavioral and proteomic research will help elucidate the factors involved in anxiety disorder and depression. This knowledge will improve preventive strategies and lead to the development of novel treatments.

Boron-containing carbonic anhydrases inhibitors.

Over the last decades, the medicinal chemistry of boron-based compounds has been extensively explored, designing valuable small molecule drugs to tackle diseases and conditions, such as cancer, infections, inflammatory and neurological disorders. Notably, boron has proven to also be a valuable element for the development of inhibitors of the metalloenzymes carbonic anhydrases (CAs), a class of drug targets with significant potential in medicinal chemistry. Incorporating boron into carbonic anhydrase inhibitors (CAIs) can modulate the ligand ability to recognize the target and/or influence selectivity towards different CA isoforms, using the tail approach and boron-based tails. The electron-deficient nature of boron and its associated properties have also led to the discovery of novel zinc-binding CAIs, such as boronic acids and the benzoxaboroles, capable of inhibiting the CAs upon a Lewis acid-base mechanism of action. The present manuscript reviews the state-of-the-art of boron-based CAIs. As research in the applications of boron compounds in medicinal chemistry continues, it is anticipated that new boron-based CAIs will soon expand the current array of such compounds. However, further research is imperative to fully unlock the potential of boron-based CAIs and to advance them towards clinical applications.

Effects of L-Dopa, SKF-38393, and quinpirole on exploratory, anxiety- and depressive-like behaviors in pubertal female and male mice.

Adolescence is a phase of substantial changes in the brain, characterized by maturational remodeling of many systems. This remodeling allows functional plasticity to adapt to a changing environment. The dopaminergic system is under morphological and physiological changes during this phase. In the present study, we investigated if changes in the dopaminergic tone alter mice behavior in a receptor and sex-specific manner, specifically at the beginning of the puberty period. We administered L-Dopa, SKF-38393 (D1 dopamine receptor agonist), and Quinpirole (D2 dopamine receptor agonist) and tested male and female mice's motor, anxiety- and depressive-like behavior. While females displayed an impaired exploratory drive, males presented an intense depressive-like response. Our results provide insights into the function of dopaminergic development in adolescent behavior and highlight the importance of studies in this time window with male and female subjects.

Excess mortality in adults from Sao Paulo during the COVID-19 pandemic in 2020: analyses of all-cause and noncommunicable diseases mortality.

In this study, we estimated the excess mortality from all-causes of death and noncommunicable diseases (NCDs) in adults living in the state of São Paulo during the COVID-19 pandemic in 2020. Number of deaths were retrieved from the Mortality Information System before (2017-2019) and during (2020) the COVID-19 pandemic, considering the following underlying causes of death: Neoplasms; Diabetes Mellitus; Circulatory System Diseases, and Respiratory System Diseases. Standardized Mortality Ratio (SMR) were calculated by dividing the mortality rates in 2020 by average mortality rates in 2017-2019, according to sex, age group, geographic location (state, capital, and Regional Health Departments). In 2020, occurred 341,704 deaths in the state of São Paulo vs 290,679 deaths in 2017-2019, representing an 18% increase in all-cause mortality (SMR 1.18) or 51,025 excess deaths during the first year of COVID-19 pandemic. The excess mortality was higher in men (186,741 deaths in 2020 vs 156,371 deaths in 2017-2019; SMR 1.18; 30,370 excess deaths) compared to women (154,963 deaths in 2020 vs 134,308 deaths in 2017-2019; SMR 1.15; 20,655 excess deaths). Regarding NCDs mortality, we observed a reduction in cancer mortality (SMR 0.98; -1,354 deaths), diseases of the circulatory system (SMR 0.95; -4,277 deaths), and respiratory system (SMR 0.88; -1,945). We found a 26% increase in Diabetes Mellitus mortality (SMR 1.26; 2885 deaths) during the pandemic year. Our findings corroborate the need to create and strengthen policies aimed at the prevention and control of NCDs, in order to mitigate the impact of future infectious disease pandemics.

Neuroimmune circuits involved in ß-lactoglobulin-induced food allergy.

Several antigens can act as allergens eliciting IgE-mediated food allergy reactions when fed to sensitized animals. One of them is ovalbumin (OVA) which is the main allergen in egg white. Allergic mice develop aversion to OVA consumption. This aversive behavior is associated with anxiety, and it can be transferred to non-sensitized mice by injection of serum of allergic mice. However, it is yet to be determined whether altered behavior is a general component of food allergy or whether it is specific for some types of allergens. Cow's milk allergy is the most prevalent food allergy that usually begins early in life and ß-lactoglobulin (BLG) is the milk component with the highest allergenicity. In this study, we investigated behavioral and neuroimmune circuits triggered by allergic sensitization to BLG. A neuroimmune conflict between aversion and reward was observed in a model of food allergy induced by BLG intake. Mice sensitized to BLG did not present aversive behavior when BLG was used for sensitization and oral challenge. Mice allergic to BLG preferred to drink the allergen-containing solution over water even though they had high levels of specific IgE, inflammatory cells in the intestinal mucosa and significant weight loss. When sensitized to OVA and challenged with the same antigen, mice had increased levels of neuron activation in the amygdala, a brain area related to anxiety. On the other hand, when mice were sensitized to OVA and received a mixture of BLG and OVA in the oral challenge, mice preferred to drink this mixture, despite their aversion to OVA, which was associated with neuron activation in the nucleus accumbens, an area related to reward behavior. Thus, the aversive behavior observed in food allergy to OVA does not apply to all antigens and some allergens may activate the brain reward system rather than anxiety and aversion. Our study provides novel insights into the neuroimmune conflicts regarding preference and avoidance to a common antigen associated with food allergy.

Characterization and effectiveness of a violet LED light for in-office whitening.

OBJECTIVES: This study characterized a violet LED light (V-LED; bright max whitening) tooth whitening device and evaluated its efficacy on stained enamel compared to hydrogen peroxide (HP). MATERIALS AND METHODS: Characterization of the V-LED beam profile was performed using a laser beam-profiler. The irradiance was measured throughout an exposure cycle at 0- and 8-mm distances using an integrating sphere and a spectral radiometer. Bovine enamel/dentin blocks stained with black tea (BT), cigarette smoke (CS), or without staining (CONT) were subjected to V-LED or 40% HP (n = 10/group). Color parameters (ΔL, Δa, Δb, and ΔE00) were measured using a digital spectrophotometer. Light transmission was estimated through 1-mm-thick bovine enamel slices (n = 5). ΔL, Δb, ΔE00, and irradiance were analyzed by two-way ANOVAs and Tukey's tests, Δa by Kruskal-Wallis and Mann-Whitney tests, and light transmission by t-test (α = 5%). RESULTS: Heterogeneous beam distribution was observed for the emitting V-LED chips. After 20 sequential exposures, irradiance levels were reduced 25-50%, regardless of the distance from V-LED. Localized irradiance values were statistically different between beam locations and different distances from the target. V-LED produced lower ΔE00, ΔL, Δa, and Δb values than HP for CONT and BT, with no differences for CS. Light transmittance decreased approximately 98% through 1-mm thick enamel. CONCLUSIONS: V-LED irradiance was heterogeneous and decreased throughout the exposure cycles and was also greatly reduced with increasing tip distance. V-LED produced a significantly lower whitening effect on BT and control teeth. CLINICAL RELEVANCE: This study contributes to the knowledge of V-LED and its clinical use.

The influence of the renewal or the single application of the peroxide gel on the efficacy and tooth sensitivity outcomes of in-office bleaching-A systematic review and meta-analysis.

OBJECTIVE: To answer the question: "Does the peroxide gel application regimen (single application vs. renewal) influence the efficacy and the tooth sensitivity outcomes of in-office tooth bleaching?" METHODS: The search was done in Pubmed, Cochrane, LILACS, Scopus, Web of Science, and EMBASE in February 2021 (updated in July 2021). Randomized clinical trials (RCT) comparing the single application vs. the renewal protocols of HP were included. The meta-analyses were performed for the objective (ΔEab ), subjective (ΔSGU) color changes, and absolute risk of tooth sensitivity (TS). Heterogeneity was evaluated using Q test (I2 ). Cochrane Collaboration tool assessed the risk of bias (RoB). The GRADE evaluated the certainty of evidence. RESULTS: Five RCT studies remained. Two studies showed high RoB, and three presented some concerns. No significant differences were observed between the protocols in terms of the ΔEab , ΔSGU, and TS. ΔEab exhibited substantial heterogeneity (I2  = 87%), while ΔSGU (I2  = 60%) and the TS (I2  = 62%) presented a moderate one. The certainty of evidence was considered low or very low, depending on the variable response and the evaluation time. CONCLUSION: The application regimen (single vs. renewal of HP) did not impact color change or the absolute risk of TS. CLINICAL SIGNIFICANCE: The renewal of bleaching gel during the in-office appointment may not be necessary. However, there is at least a low certainty of evidence. Because of this, further randomized clinical trials with appropriate methodology on this topic are encouraged.

Spontaneous ovarian hyperstimulation syndrome in a pregnant woman with hypothyroidism: a case report.

OBJECTIVE: To study a rare case of spontaneous ovarian hyperstimulation syndrome in a naturally conceived pregnancy associated with overt hypothyroidism. DESIGN: Case report. SETTING: Endocrinology private practice. PATIENTS: A 32-year-old woman who was 13 weeks pregnant with bilaterally enlarged ovaries presumed to be secondary to hypothyroidism. INTERVENTIONS: Administration of levothyroxine and titration of the dose. MAIN OUTCOME MEASURES: Regression of signs and symptoms of spontaneous ovarian hyperstimulation syndrome after 12 weeks of therapy. RESULTS: The patient was diagnosed with severe hypothyroidism, as confirmed by her elevated thyroid-stimulating hormone level. Ultrasound evaluation revealed ovarian enlargement secondary to multiple contiguous cysts with anechoic content. The patient was administered levothyroxine 175 µg/day. Results of hormonal studies demonstrated thyroid function normality at week 12 after treatment. Incomplete regression of ovarian cysts was also noticed within this period. At week 37, the patient developed preeclampsia, and cesarean delivery was recommended. An 8-month postpartum ultrasound evaluation revealed complete regression of the cysts. CONCLUSIONS: Spontaneous ovarian hyperstimulation syndrome secondary to hypothyroidism may be the cause of ovarian enlargement, and levothyroxine replacement seems an appropriate primary therapeutic option. Proper endocrinological assessment of patients is recommended as it may avoid unfavorable outcomes.

Chagas disease is not associated with diabetes, metabolic syndrome, insulin resistance and beta cell dysfunction at baseline of Brazilian Longitudinal Study of Adult Health (ELSA-Brasil).

Chagas disease (ChD) affects millions of people worldwide, being endemic in Latin America and emerging in the United States and Europe. Classically described as targeting the heart and gastrointestinal tract, Trypanosoma cruzi parasitism leads to structural and pro-inflammatory changes in the adipose tissue and pancreas. The effects of these changes on insulin resistance (IR), beta cell dysfunction, diabetes mellitus (DM),and metabolic syndrome (MS) are unclear. We aim to evaluate the association of ChD with DM, IR, beta cell dysfunction and MS in the baseline of multi-centric cohort study 'Brazilian Longitudinal Study of Adult Health' (ELSA-Brasil). This cross-sectional analysis included 14,922 (98%) participants of ELSA-Brasil at baseline. To investigate the associations of ChD with DM, IR (assessed by HOMA-IR) and beta cell dysfunction (assessed by HOMA beta), and MS we fitted logistic regression models including socio-demographic and anthropometric variables, health-related conditions and laboratory results. ChD, defined by positive serology, was prevalent in 1.9% (n = 283) of the sample, 17.3% (n = 49) of whom had cardiomyopathy. DM prevalence was 17.25% (n = 2574) and was not different among those with and without ChD (20.5% vs 17.2%; p = 0.28). Fasting and 2 h-blood glucose after a 75 g anhydrous glucose were slightly higher among participants positive for ChD, when compared with those with negative serology (102 mg/dL versus 100 mg/dL, respectively; and 127 mg/dL versus 124 mg/dL, respectively), only in univariate analysis. There was no significant association between these variables and ChD after adjustments. In addition, there was no significant association between DM, IR, beta cell dysfunction or MS and ChD (without and with cardiomyopathy). Our results showed that ChD, regardless of the presence of cardiomyopathy, is not associated with DM, IR, beta cell dysfunction or MS. These findings suggest the parasitism of the adipose tissue and pancreas in Chagas disease do not translate into clinically relevant glucose abnormalities.

Use of antioxidants to restore bond strength after tooth bleaching with peroxides.

This review compiles the literature on the antioxidants used after tooth bleaching with either low or high-concentrated carbamide and hydrogen peroxide to recover the bond strength. Antioxidants used in bleached teeth are mainly natural and non-enzymatic, except for catalase. Commonly, antioxidants are applied to remove any reactive oxygen species (ROS) residues left from bleaching gels, which adversely affect adhesive procedures, such as restorations or orthodontic brackets bonding. Even though sodium ascorbate, the most thoroughly investigated antioxidant, showed the most efficient bond strength recovery at 10% concentration, its performance depends on the type of solution and the application time. Natural extracts, such as proanthocyanidins and green tea, showed satisfactory results in the reversal of bond strength at 5% and 10% concentrations, respectively. Sodium ascorbyl phosphate, α-tocopherol, and catalase exhibited promising results, but further research is required. The adhesive system type plays an important role in the outcome of enamel bond strength after the antioxidant application. The postponement of either restorations or orthodontic brackets cementation following bleaching procedures seems to be efficiently replaced by antioxidant application prior to bonding procedures. However, the efficacy of using an antioxidant to recover bond strength depends on its type and application time.

Effects of dental bleaching protocols with violet radiation on the color and chemical composition of stained bovine enamel.

OBJECTIVES: To evaluate the bleaching efficacy of a violet radiation (VR) combined or not with bleaching gels on the color and mineral content of stained teeth. MATERIAL AND METHODS: Enamel/dentin blocks were obtained and stained (n = 50) with coffee, red wine, tobacco smoke, or were left non-stained. The stained or not-stained blocks (n = 10) were distributed into five bleaching groups (n = 10): VR, CP (37 % carbamide peroxide), VR/CP, HP (35 % hydrogen peroxide), and VR/HP. Color (ΔE00, ΔL, Δa, and Δb) and whiteness index (ΔWID) changes were evaluated after staining and after bleaching using a spectrophotometer. Calcium (Ca), phosphorous (P), and Ca/P contents (in wt%) were measured after bleaching using energy-dispersive X-ray spectroscopy (EDS). Data was statistically analyzed (α = 0.05) using two-way ANOVA and Tukey tests (ΔE00, ΔWID, ΔL, Δb, wt%) or Kruskal-Wallis and Dunn tests (Δa). RESULTS: VR alone caused higher colorimetric changes on coffee, tobacco and red wine-stained groups compared to non-stained enamel (p < 0.05). VR/CP exhibited higher colorimetric changes compared to CP in coffee and non-stained groups. The VR/CP, HP and VR/HP groups exhibited no change differences (p > 0.05). No differences were observed for the wt% of Ca, P and Ca/P between the groups. CONCLUSIONS: The violet radiation was more effective in bleaching stained rather than non-stained teeth. VR combined with 37 % carbamide peroxide was as effective as the HP agent. Besides, no adverse effects could be observed in the enamel mineral content, regardless of the bleaching protocol tested, according to the EDS semi-quantitative analysis.

Case Report: Atypical Cutaneous Leishmaniasis in a Patient with Mixed Leishmania guyanensis and Leishmania amazonensis Infection.

The disseminated form of leishmaniasis is a serious and rare disease, being diagnosed in 2% of the cutaneous cases registered per year in Brazil. The main characteristic is the appearance of multiple pleomorphic lesions on the cutaneous surface. A 68-year-old male from the rural area of Tocantins, Brazil, presented atypical disseminated cutaneous leishmaniasis (ACL). The clinical course and histopathological and immunological findings presented a mixed pattern that hindered diagnosis and therapeutic management. Molecular typing revealed a mixed infection with Leishmania (V.) guyanensis and Leishmania (L.) amazonensis. Molecular identification of the agents responsible for ACL is important for adequate therapeutic planning, minimizing the possibility of sequellae that impact the quality of life of the patient.

Clinical epidemiology of Clostridium difficile infection among hospitalized patients with antibiotic-associated diarrhea in a university hospital of Brazil.

A cohort of 110 adult individuals was analyzed to compare clinical characteristics of hospitalized patients who received antibiotics and developed Clostridium difficile infection (CDI) with those who received antibiotics and did not develop the disease in a university Hospital in Brazil. CDI was diagnosed by toxigenic culture and C. difficile isolates were characterized by PCR ribotyping. Stool samples were also screened for Clostridium perfringens, methicillin-resistant Staphylococcus aureus (MRSA) and Klebsiella oxytoca. The prevalence of CDI among patients with AAD was 31.8%. C. difficile diarrhea was significantly associated with the severity of underlying comorbidities at admission (OR = 1.21; 95% CI, 1.04-1.40) and with the number of antibiotics used during hospitalization (OR = 1.43; 95% CI, 1.07-1.92). Diabetes mellitus was markedly associated with a higher risk of death in patients with AAD (OR = 6.38; 95% CI, 1.33-30.7). PCR ribotypes 014/020 and 106 (20.6% each) were the most common among the isolates. Binary toxin-encoding gene (cdtB) was detected in six samples, but previously described hypervirulent ribotypes 027 and 078 were not found. K. oxytoca and enterotoxigenic C. perfringens were not detected, while only one patient (0.9%) was positive for MRSA. Our results indicate that comorbidity severity and the number of antibiotics used during hospitalization are strong independent predictors of nosocomial C. difficile diarrhea. Diabetes was associated with a higher mortality among patients with AAD. A huge diversity of C. difficile ribotypes was observed in our study, although classical hypervirulent strains were not observed.

American tegumentary leishmaniasis: epidemiological and molecular characterization of prevalent Leishmania species in the State of Tocantins, Brazil, 2011-2015.

Determination of the epidemiological profile of the American tegumentary leishmaniasis (ATL) and identification of Leishmania species that are prevalent in the State of Tocantins were carried out through a retrospective and descriptive study based on data reported in SINAN, in the period from 2011 to 2015. Molecular techniques such as PCR-RFLP and PCR-G6PD to amplify Leishmania DNA were performed on stored on Giemsa-stained slides from lesion scarifications of ATL patients who were amastigote-positive by the direct microscopic examination. There were 1,434 ATL cases in Tocantins reported in this period. The highest incidence was reported in men aged over 60 years, rural residents, the most affected ethnic group was mixed ethnicity (mixed black and white) and the ones with lower education. The predominant clinical form was cutaneous, being diagnosed mainly by laboratory methods. Pentavalent antimonial was effective in resolving cases. The predominant species found in 271 analyzed samples from 32 municipalities located in 8 different health regions of Tocantins was Leishmania (Viannia) braziliensis. Identifying the epidemiological profile and characterizing the Leishmania spp species on regional level is essential to establish control and prevention behaviors, minimizing the number of cases and treatment resistance, recurrence and evolution to mucosal forms.

The effectiveness of postoperative physical therapy treatment in patients who have undergone arthroscopic partial meniscectomy: systematic review with meta-analysis.

STUDY DESIGN: Systematic review with meta-analysis. OBJECTIVES: To evaluate the effectiveness of postoperative physical therapy treatment for patients who have undergone arthroscopic partial meniscectomy. BACKGROUND: There is no consensus on which treatment is best for patients post meniscectomy. METHODS: A search for articles published from 1950 to March 2013 was conducted in the MEDLINE, Embase, CINAHL, LILACS, SciELO, IBECS, Scopus, Web of Science, PEDro, Academic Search Premier, and Cochrane Central Register of Controlled Trials databases. The key words were physiotherapy, physical therapy modalities, exercise therapy, rehabilitation, knee, placebo, groups, tibial meniscus, meniscus, arthroscopy, meniscectomy, partial meniscectomy, randomized controlled trial, controlled clinical trial, randomized, systematic review, and meta-analysis. RESULTS: Eighteen randomized controlled trials were included in the review, 6 of which were included in the meta-analysis. Outpatient physical therapy plus a home exercise program, compared to a home program alone, improved function compared to a home program alone (mean difference, 10.3; 95% confidence interval: 1.3, 19.3; P = .02) and knee flexion range of motion (mean difference, 9.1; 95% confidence interval: 3.7, 14.5; P = .0009). Inpatient physical therapy alone compared to inpatient plus outpatient physical therapy reduced the likelihood of effusion (odds ratio = 0.25; 95% confidence interval: 0.10, 0.61; P = .003). CONCLUSION: Physical therapy associated with home exercises seems to be effective in improving patient-reported knee function and range of motion in patients post-arthroscopic meniscectomy, although the included randomized controlled trials were classified from moderate to high risk of bias and should be interpreted with caution. LEVEL OF EVIDENCE: Therapy, level 1a-.

The contribution of FTO and UCP-1 SNPs to extreme obesity, diabetes and cardiovascular risk in Brazilian individuals.

BACKGROUND: Obesity has become a common human disorder associated with significant morbidity and mortality and adverse effects on quality of life. Sequence variants in two candidate genes, FTO and UCP-1, have been reported to be overrepresented in obese Caucasian population. The association of these genes polymorphisms with the obesity phenotype in a multiethnic group such as the Brazilian population has not been previously reported. METHODS: To assess the putative contribution of both FTO and UCP-1 to body mass index (BMI) and cardiovascular risk we genotyped SNPs rs9939609 (FTO) and rs6536991, rs22705565 and rs12502572 (UCP-1) from 126 morbidly obese subjects (BMI 42.9 ± 5.6 kg/m2, mean ± SE) and 113 normal-weight ethnically matched controls (BMI 22.6 ± 3.5 kg/m2, mean ± SE). Waist circumference, blood pressure, glucose and serum lipids were also measured. Each sample was also genotyped for 40 biallelic short insertion/deletion polymorphism (indels) for ethnic assignment and to estimate the proportion of European, African and Amerindian biogeographical ancestry in the Brazilian population. RESULTS: Cases did not differ from controls in the proportions of genomic ancestry. The FTO SNP rs9939609 and UCP-1 SNP rs6536991 were significantly associated with BMI (p= 0.04 and p<0.0001 respectively). An allele dose dependent tendency was observed for BMI for rs6536991 sample of controls. No other significant associations between any SNP and hypertension, hyperlipidemia and diabetes were noted after correction for BMI and no significant synergistic effect between FTO and UCP-1 SNPs with obesity were noted. There was not an association between rs9939609 (FTO) and rs6536991 (UCP-1) in with maximum weight loss after 1 year in 94 obese patients who underwent bariatric surgery. CONCLUSION: Our data are consistent with FTO rs9939609 and UCP-1 rs6536991 common variants as contributors to obesity in the Brazilian population.

Miocardiopatia periparto / Peripartum cardiomyopathy

A miocardiopatia periparto (MCPP) é doença rara, reconhecida como entidade distinta das cardiomiopatias preexistentes, de ocorrência em mulheres previamente saudáveis, durante o período periparto. É pouco conhecida em relação a sua etiologia, risco e prognóstico. As manifestações clínicas mais comuns são as da insuficiência cardíaca sistólica. Sua terapia farmacológica convencional inclui diuréticos, digoxina, inibidores da enzima conversora de angiotensina, bloqueadores dos receptores de angiotensina e bloqueadores beta-adrenérgicos. Os pacientes refratários à terapia farmacológica convencional requerem o suporte circulatório mecânico e o transplante cardíaco. Não existe consenso sobre os riscos de futuras gravidezes em pacientes com MCPP prévia.

Peripartum cardiomyopathy (PPCM) is a rare disease, recognized as a distinct entity from preexisting cardiomyopathy. It occurs in previously healthy woman, during the peripartum period. PPCM is still a little known disease concerning its etiology, risk and prognosis. The most common clinical manifestations are those of systolic heart dysfunction. The objective of the study is to review the scientific literature about the several aspects of PPCM. A total of 19 publications were evaluated. The conventional therapy for congestive heart failure includes diuretics, digoxin, angiotensin-converting enzyme inhibitors (ACEI), angiotensin II receptor blockers (ARB) and beta-adrenergic blockers. For those patients who are resistant to all conventional pharmacological therapy, the viable options are cardiac transplant and mechanical circulation support. There is no consensus about the recommendations on risk of future pregnancies in these patients. Results demonstrate the need for more studies to the understanding of this disease etiology, epidemiology and prognosis.

Miocardiopatia periparto: aspectos relevantes / Peripartum cardiomyopathy: relevant aspects

A miocardiopatia periparto constitui entidade clínica rara, caracterizada por dilatação cardíaca e manifestações de insuficiência cardíaca grave, capaz de evoluir de forma fatal. Ocorre nos meses finais da gestação ou precocemente no puerpério. Sua etiologia e epidemiologia ainda são pouco conhecidas. Há grande discrepância nos prognósticos observados em relatos de caso, variando desde recuperação completa da função ventricular até fatalidade. Neste artigo é relatada a apresentação da doença de forma típica. O objetivo é enfatizar sua importância para que seja instituída precocemente sua terapêutica, evitando assim sua progressão para formas graves.

Peripartum cardiomyopathy (PPCM) is a rare clinical condition characterized by cardiac dilation and signs of severe heart failure and can be fatal. Its main characteristic is to affect women in the final months of pregnancy or early puerperium. Although the high morbidity and mortality, its etiology and epidemiology are poorly known. However, the outcome reports differ widely from complete recovery to death. The article reports a case to illustrate a typical manifestation of the disease. Our objective is to emphasize the importance of the theme not only to cardiologists but also to obstetricians, as the early therapy is the most important way to prevent the progression to severe conditions. Therefore the diagnosis of PPCM requires a lot of care and attention, and preventive counseling after PPCM is important due the increased risk for recurrence in a subsequent pregnancy.

Nephrogenic diabetes insipidus (NDI): clinical, laboratory and genetic characterization of five Brazilian patients.

INTRODUCTION: Nephrogenic diabetes insipidus is characterized by a lack of response in the distal nephron to the antidiuretic hormone arginine vasopressin. Manifestations include polyuria, polydipsia, hyposthenuria, recurrent episodes of dehydration and fever and growth failure. Most cases are caused by mutations in the AVPR2 gene. The mutant receptors are trapped intracellularly. METHOD: We studied five boys using clinical, laboratory and molecular data. The mean age at diagnosis was 14.6 months (range 6 to 24) and 12.2 years (7.8 to 19) after the follow-up period. The mean period of follow-up was 132.2 +/- 50.9 months. RESULTS: The geometric means of the z-scores of weight and stature were -4.5 and -3.6, respectively, at diagnosis. At the last medical appointment, the z-scores of weight and stature were -0.3 and -0.9, respectively. Three patients were diagnosed with ureterohydronephrosis and exhibited increased post-void urine volume. Mutations in the AVPR2 gene were found in all patients, and the carrier status was confirmed in four of five cases. Two unrelated children presented identical mutations (S167L) in arginine vasopressin R2. Two of the patients had a mutation that has already been described in other Brazilian families (R337X), and one patient showed a de novo mutation (Y128D) in arginine vasopressin R2, since his mother's molecular analysis was normal. The recurrence risk for this family was significantly reduced. CONCLUSION: This study reports the clinical and laboratory characterization of Nephrogenic diabetes insipidus and reiterates the importance of the genetic basis that underlies the disease diagnosis and genetic counseling.

Novel mutations of the BSCL2 and AGPAT2 genes in 10 families with Berardinelli-Seip congenital generalized lipodystrophy syndrome.

CONTEXT: Congenital generalized lipodystrophy, or Berardinelli-Seip syndrome, is a rare autosomal recessive disease caused by mutations in either the BSCL2 or AGPAT2 genes. This syndrome is characterized by an almost complete loss of adipose tissue usually diagnosed at birth or early infancy resulting in apparent muscle hypertrophy. Common clinical features are acanthosis nigricans, hepatomegaly with or without splenomegaly and high stature. Acromegaloid features, cardiomyopathy and mental retardation can also be present. DESIGN: We investigated 11 kindreds from different geographical areas of Brazil (northeast and southeast). All coding regions as well as flanking intronic regions of both genes were examined. Polymerase chain reaction (PCR) amplifications were performed using primers described previously and PCR products were sequenced directly. RESULTS: Four AGPAT2 and two BSCL2 families harboured the same set of mutations. BSCL2 gene mutations were found in the homozygous form in four kindreds (c.412C>T c.464T>C, c.518-519insA, IVS5-2A>G), and in two kindreds compound mutations were found (c.1363C>T, c.424A>G). In the other four families, one mutation of the AGPAT2 gene was found (IVS3-1G>C and c.299G>A). CONCLUSIONS: We have demonstrated four novel mutations of the BSCL2 and AGPAT2 genes responsible for Berardinelli-Seip syndrome and Brunzell syndrome (AGPAT2-related syndrome).