Nephrotic syndrome in the elderly: epidemiological aspects, clinical data, and renal biopsy findings

Nephrotic syndrome is the most common clinical presentation of glomerular disease in elderly patients, and renal biopsy is an important diagnostic resource. The aim of this study was to describe nephrotic syndrome among elderly patients in Brazil, focusing on tubulointerstitial and vascular involvement. This was a retrospective study of patients over 65 years of age with nephrotic syndrome who underwent renal biopsy between January 2012 and December 2019. Of the 123 renal biopsies that occurred during the study period, 44 (35.8%) were performed for the investigation of nephrotic syndrome. Among those 44 cases, the main etiologies were membranous nephropathy in 13 cases (29.5%), amyloidosis in ten (22.7%), non-collapsing focal segmental glomerulosclerosis (FSGS) in four (9.1%), and collapsing FSGS in four (9.1%). Patients with minimal change disease (MCD) had the lowest degree of interstitial fibrosis compared with the other glomerulopathies, and histological signs of acute tubular necrosis (ATN) were less common among those with amyloidosis than among those with membranous nephropathy, FSGS, or MCD (P=0.0077). Of the patients with ATN, the frequency of acute kidney injury (AKI) was highest in those with MCD (P<0.001). All patients had some degree of vascular involvement, regardless of the type of glomerulopathy. In conclusion, the second most common cause of nephrotic syndrome in this population was amyloidosis, and acute interstitial tubule involvement was more marked in MCD. Vascular involvement is something that cannot be dissociated from the age of the patient and is not only due to the underlying glomerulopathy.

Method of determining the location of the sexual neurovascular bundle (internal pudendal artery, internal pudendal vein and pudendal nerve) / Método para determinar la ubicación del haz neurovascular sexual (vena y arteria pudenda interna y nervio pudendo)

Disorders in the course of the neurovascular bed of the sexual neurovascular bundle (NVB) entail problems of gynecological, andrological and urological nature, for example, the state of impotence in men. The aim of the study was to establish a method to determine a projection. The Arteria pudenda interna, Vena pudenda interna and Nervus pudendus (sexual neurovascular bundle or NVB) from the infrapiriform foramen to the Alcock's canal (pudendal canal) in which the pudendal neurovascular bundle runs. Topographic and anatomical study was performed on 15 corpses without organ complex (remote shore): 9-from men and 6-women, aged 36 to 74 years. Each object of study (corpse) included 2 pairs of sexual NVB, a total of 30 investigated. The information obtained on the projection branches of the pudendal nerve, and pudendal internal artery and pudendal internal vein from infrapiriform foramen to the entrance of the pudendal canal. A method for determining the projection of sexual NVB in the gluteal region was developed. The projection of Arteria pudenda interna, Vena pudenda interna and Nervus pudendus from the infrapiriform foramen in the gluteal region and to the entrance of the pudendal canal is determined. The morphometric data necessary for the mathematical equation developed by us for the calculation of the boundaries of the projection of the desired plane in the course of the sexual NVB are obtained . Using these data in the method of mathematical calculation developed by us using the formula C'c' = 0,2679 x (A'G-AD+3), we determined the projection of the figure, in the form of a trapezoid, in the center of which the projection of the sexual NVB is determined.A method for determining the projection of the sexual neurovascular bundle in the gluteal region for diagnosis and therapeutic effects on sexual NPS was developed.

Los trastornos en el curso de las estructuras del haz neurovascular sexual conllevan problemas de naturaleza ginecológica, andrológica y urológica, por ejemplo, el estado de impotencia en los hombres. El objetivo de este estudio fue establecer un método para determinar una proyección de los vasos pudendos internos y el nervio pudendo (haz neurovascular sexual o HNV) desde el foramen infrapiriforme hasta el canal de Alcock (canal pudendo). Se realizó un estudio topográfico y anatómico en 15 cadáveres: 9 hombres y 6 mujeres, entre 36 y 74 años. Se analizaron 30 muestras, cada cadáver incluyó 2 pares de HNV sexuales. Se obtuvo información sobre las ramas de proyección de la arteria, y vena pudenda interna y del nervio pudendo, desde el foramen infrapiriforme hasta la entrada al canal pudendo. Se desarrolló un método para determinar la proyección de NVB sexual en la región glútea. La proyección de la vena pudenda interna y del nervio pudendo se determinó desde el foramen infrapiriformis en la región glútea, hasta la entrada del canal pudendo. Se obtuvieron datos morfométricos necesarios para la ecuación matemática y obtener el cálculo de los límites de la proyección del plano deseado en el curso de la HNV sexual. Usando estos datos se utilizó la fórmula C'c '= 0,2679 x (A'G-AD + 3), y se realizó la proyección de la figura, en forma de trapecio, en el centro del cual se determinó la proyección de la HNV sexual. Se desarrolló un método para la proyección del haz neurovascular sexual en la región glútea, en el diagnóstico y los efectos terapéuticos sobre el NPS sexual.

Heterogeneity in the aetiology of diabetes mellitus in young adults: A prospective study from north India

Background & objectives: In contrast to Caucasians of European origin, the aetiology of diabetes mellitus (DM) in young adults in other ethnic groups, including Indians is likely to be heterogeneous and difficult to determine. This study was undertaken to determine the aetiology of diabetes in young Indian adults using a protocol-based set of simple clinical and investigation tools. Methods: In this prospective study, 105 Indian young adults with diabetes (age at onset 18-35 yr; duration <2 yr) were studied for a period of 1-3 years. Pancreatic imaging, fasting C-peptide, islet antibodies (against glutamic acid decarboxylase, tyrosine phosphatase and zinc transporter-8) and mitochondrial A3243G mutational analysis were performed in all patients. Four patients were screened for maturity-onset diabetes of the young (MODY) using next-generation sequencing. Results: Type 1 and type 2 diabetes mellitus (T1DM and T2DM) were equally frequent (40% each), followed by fibrocalculous pancreatic diabetes (FCPD, 15%). Less common aetiologies included MODY (2%), mitochondrial diabetes (1%) and Flatbush diabetes (2%). There was considerable phenotypic overlap between the main aetiological subtypes. Elevated islet antibodies were noted in 62 per cent of T1DM patients [positive predictive value (PPV) 84%; negative predictive value (NPV) 78%] while low plasma C-peptide (<250 pmol/l) was present in 56 per cent of T1DM patients [PPV 96% (after excluding FCPD), NPV 72%]. Using these tests and observing the clinical course over one year, a final diagnosis was made in 103 (99%) patients, while the diagnosis at recruitment changed in 23 per cent of patients. Interpretation & conclusions: The aetiology of diabetes in young adults was heterogeneous, with T1DM and T2DM being equally common. FCPD was also frequent, warranting its screening in Indian patients. Testing for islet antibodies and C-peptide in this age group had good PPV for diagnosis of T1DM.

Prevalencia de cardiopatía isquémica asintomática en pacientes con diabetes mellitus tipo 2 / Prevalence of asymptomatic ischaemic heart disease in patients with type 2 diabetes mellitus

Resumen Introducción: La enfermedad cardiovascular es la causa principal de muerte en pacientes con diabetes mellitus. La prevalencia de cardiopatía isquémica asintomática es más alta en pacientes diabéticos que en no diabéticos y se asocia a peor pronóstico. Objetivo: Identificar la prevalencia de cardiopatía isquémica asintomática en pacientes con diabetes mellitus tipo 2 en un hospital de tercer nivel de atención de Guatemala y analizar la posible asociación de dicha enfermedad con características epidemiológicas, clínicas y metabólicas. Métodos: Estudio de corte transversal en el que se estudió una muestra de 92 pacientes diabéticos seleccionados de forma aleatoria simple. Se realizó electrocardiograma, que cuando fue negativo para isquemia ameritó prueba de esfuerzo, o de lo contrario, ecocardiograma de estrés con dobutamina. Resultados: La edad media de los participantes fue de 57 años, 88% de los cuales eran mujeres; la duración media de la diabetes fue 7 años. Se encontró cardiopatía isquémica asintomática en el 22,8% de los casos. No se hallaron posibles asociaciones entre cardiopatía isquémica asintomática y edad, sexo, enfermedad arterial periférica, índice de masa corporal, índice tobillo-brazo, hipertensión arterial, dislipidemia, tabaquismo activo, sedentarismo, sobrepeso/obesidad, alcoholismo, glucosa en ayunas, hemoglobina glicosilada, colesterol total, colesterol HDL, colesterol LDL, ácido úrico, creatinina, tasa de filtrado glomerular y microalbuminuria. Conclusiones: La prevalencia de cardiopatía isquémica asintomática en la población estudiada con diabetes mellitus tipo 2 fue de 22,8%. No se encontraron posibles asociaciones de cardiopatía isquémica asintomática con las variables estudiadas.

Abstract Introduction: Cardiovascular disease is the main cause of death in patients with diabetes mellitus. The prevalence of asymptomatic ischaemic heart disease is higher in diabetic patients than in non-diabetic ones, and is associated with a worse prognosis. Objective: To determine the prevalence of asymptomatic ischaemic heart disease in patients with type 2 diabetes mellitus in a third level of care hospital in Guatemala, as well as to analyse the possible relationship of this disease with epidemiological, clinical, and metabolic characteristics. Methods: A cross-sectional study was conducted on a sample of 92 randomly selected diabetic patients. An electrocardiogram was performed, which when it was negative for ischaemia, an exercise stress test or a dobutamine stress echocardiogram was performed. Results: The mean age of the participants was 57 years, 88% of whom were women. The mean duration of the diabetes was 7 years. Asymptomatic ischaemic heart disease was found in 22.8% of case. No significant associations were found between ischaemic heart disease and age, gender, peripheral arterial disease, body mass index, ankle-brachial index, arterial hypertension, dyslipidaemia, active smoking, sedentarism, overweight/obesity, alcoholism, fasting glucose, glycosylated haemoglobin, total cholesterol, HDL-cholesterol, LDL-cholesterol, uric acid, creatinine, glomerular filtration rate, and urine microalbumin. Conclusions: The prevalence of asymptomatic ischaemic heart disease was 22.8% in the population studied with type 2 diabetes mellitus. No significant associations were found between ischaemic heart disease and the variables studied.

Circular RNA hsa_circ_0000523 regulates the proliferation and apoptosis of colorectal cancer cells as miRNA sponge

Among the novel class of endogenous long non-coding RNAs, circular RNA (circRNA) is known as a key regulator in the development and progression of different cancers. Its function and mechanism in the tumorigenesis of colorectal cancer, however, has not been well studied. This study thus aimed to investigate potential regulation of colorectal cancer by circRNAs and the corresponding regulatory mechanism. We demonstrated that the expression of circRNA hsa_circ_0000523 (also known as circ_006229) was down-regulated in different colorectal cancer cell lines. It was also found that interference of hsa_circ_0000523 induced proliferation and suppressed apoptosis of colorectal cancer cells, the proliferation rate of which was reduced by the overexpression of hsa_circ_0000523. In addition, we found that miR-31 could recognize hsa_circ_0000523 sequence and that it acted as a "sponge" of miR-31, indirectly regulating Wnt/β-catenin signaling pathway, which was involved in the progression of colorectal cancer. The results suggested that the expression of hsa_circ_0000523 correlated to the tumorigenesis of colorectal cancer cells. In addition, as a sponge of miR-31, the low level of hsa_circ_0000523 led to activation of Wnt/β-catenin signaling pathway, inducing the subsequent progress of colorectal cancer.

Antiviral activity of shikonin ester derivative PMM-034 against enterovirus 71 in vitro

Human enterovirus 71 (EV71) is the major causative agent of hand, foot, and mouth disease (HFMD), particularly in infants and children below 4 years of age. Shikonin is a bioactive compound with anti-inflammatory, antiviral, and antibacterial activities derived from the roots of the Chinese medicinal herb Lithospermum erythrorhizon. This study aimed to examine the antiviral activity of PMM-034, a shikonin ester derivative, against EV71 in rhabdomyosarcoma (RD) cells. Cytotoxicity of PMM-034 on RD cells was determined using WST-1 assay. Dose- and time-dependent effects of PMM-034 on EV71 replication in RD cells were determined using plaque reduction assay. mRNA expression levels of EV71/VP1 and pro-inflammatory cytokines (IL-1β, IL-6, IL-8, and TNF-α) were determined by real-time RT-PCR, and EV71/VP1 and phospho-p65 protein expressions were determined by western blot analysis. PMM-034 exhibited only weak cytotoxicity against RD cells. However, PMM-034 exhibited significant antiviral activity against EV71 in RD cells with 50% inhibitory concentration of 2.31 μg/mL. The VP1 mRNA and protein levels were significantly reduced in cells treated with PMM-034. Furthermore, relative mRNA expression levels of IL-1β, IL-6, IL-8, and TNF-α significantly decreased in the cells treated with PMM-034, while the phospho-p65 protein expression was also significantly lower in the treated cells. These results indicated that PMM-034 suppressed the expressions of pro-inflammatory cytokines in RD cells, exhibiting antiviral activity against EV71, as evidenced by the reduced VP1 mRNA and protein levels in PMM-034-treated cells. Thus, PMM-034 is a promising candidate for further development as an EV71 inhibitor.

More than 10 years survival with sequential therapy in a patient with advanced renal cell carcinoma: a case report

Although radical nephrectomy alone is widely accepted as the standard of care in localized treatment for renal cell carcinoma (RCC), it is not sufficient for the treatment of metastatic RCC (mRCC), which invariably leads to an unfavorable outcome despite the use of multiple therapies. Currently, sequential targeted agents are recommended for the management of mRCC, but the optimal drug sequence is still debated. This case was a 57-year-old man with clear-cell mRCC who received multiple therapies following his first operation in 2003 and has survived for over 10 years with a satisfactory quality of life. The treatments given included several surgeries, immunotherapy, and sequentially administered sorafenib, sunitinib, and everolimus regimens. In the course of mRCC treatment, well-planned surgeries, effective sequential targeted therapies and close follow-up are all of great importance for optimal management and a satisfactory outcome.

Serotonin regulates osteoblast proliferation and function in vitro

The monoamine serotonin (5-hydroxytryptamine, 5-HT), a well-known neurotransmitter, also has important functions outside the central nervous system. The objective of this study was to investigate the role of 5-HT in the proliferation, differentiation, and function of osteoblasts in vitro. We treated rat primary calvarial osteoblasts with various concentrations of 5-HT (1 nM to 10 µM) and assessed the rate of osteoblast proliferation, expression levels of osteoblast-specific proteins and genes, and the ability to form mineralized nodules. Next, we detected which 5-HT receptor subtypes were expressed in rat osteoblasts at different stages of osteoblast differentiation. We found that 5-HT could inhibit osteoblast proliferation, differentiation, and mineralization at low concentrations, but this inhibitory effect was mitigated at relatively high concentrations. Six of the 5-HT receptor subtypes (5-HT1A, 5-HT1B, 5-HT1D, 5-HT2A, 5-HT2B, and 5-HT2C) were found to exist in rat osteoblasts. Of these, 5-HT2A and 5-HT1B receptors had the highest expression levels, at both early and late stages of differentiation. Our results indicated that 5-HT can regulate osteoblast proliferation and function in vitro.

Effects of sirolimus alone or in combination with cyclosporine A on renal ischemia/reperfusion injury

Calcineurin inhibitors exacerbate ischemic injury in transplanted kidneys, but it is not known if sirolimus protects or exacerbates the transplanted kidney from ischemic injury. We determined the effects of sirolimus alone or in combination with cyclosporin A (CsA) on oxygenated and hypoxic/reoxygenated rat proximal tubules in the following in vitro groups containing 6-9 rats per group: sirolimus (10, 50, 100, 250, 500, and 1000 çg/mL); CsA (100 µg/mL); sirolimus (50 and 250 çg/mL) + CsA (100 µg/mL); control; vehicle (20 percent ethanol). For in vivo studies, 3-week-old Wistar rats (150-250 g) were submitted to left nephrectomy and 30-min renal artery clamping. Renal function and histological evaluation were performed 24 h and 7 days after ischemia (I) in five groups: sham, I, I + SRL (3 mg·kg-1·day-1, po), I + CsA (3 mg·kg-1·day-1, sc), I + SRL + CsA. Sirolimus did not injure oxygenated or hypoxic/reoxygenated proximal tubules and did not potentiate the tubular toxic effects of CsA. Neither drug affected the glomerular filtration rate (GFR) at 24 h. GFR was reduced in CsA-treated rats on day 7 (0.5 ± 0.1 mL/min) but not in rats receiving sirolimus + CsA (0.8 ± 0.1 mL/min) despite the reduction in renal blood flow (3.9 ± 0.5 mL/min). Acute tubular necrosis regeneration was similar for all groups. Sirolimus alone was not toxic and did not enhance hypoxia/reoxygenation injury or CsA toxicity to proximal tubules. Despite its hemodynamic effects, sirolimus protected post-ischemic kidneys against CsA toxicity.

Current treatment and prognosis of Wilms' tumor.

Thanks to the nationally and internationally organized efforts refinements in the therapy of Wilms' tumor have allowed restructuring and reduction of therapeutic strategies. A decrease in tumor relapse and long term sequelae are the immediate goals which will no doubt be the result of tailoring chemotherapy and radiation therapy exposure together with improved surgical techniques and outstanding supportive care.

Enhanced eosinophil luminol-dependent chemiluminescence and complement receptor expression by platelet-activating factor and interleukin-5.

The cytokine interleukin-5 (IL-5) and the lipid mediator platelet-activating factor (PAF) have both been shown to be involved in eosinophil differentiation and activation. We have measured and compared the effect of PAF and IL-5 on human eosinophils in terms of their luminol-dependent chemiluminescence (CL) response and their expression of complement receptors, CR1 and CR3. Both IL-5 and PAF enhanced the eosinophil CL response. The optimal concentrations were 40 U/ml for IL-5, and 10(-6) M for PAF. The priming effect of IL-5 was slow and reached a maximal response after 90 minutes incubation. In contrast, the effect of PAF peaked early and declined during incubation. In the complement receptor study, only PAF was able to enhance CR3 expression (p < 0.05) while the effect of IL-5 on eosinophil complement receptor expression was negligible. These results provide evidence that both inflammatory mediator (PAF) and cytokine (IL-5) can activate eosinophils but the effects of IL-5 and PAF on eosinophil CL response appear to be distinct. The activation of eosinophils by PAF and IL-5 may occur through different mechanisms.

Retinoblastoma: a review.

Retinoblastoma is the most common primary ocular malignancy in childhood, usually occurring below the age of five. Recent advances in molecular biology have enabled understanding of retinoblastoma tumorigenesis as well as detecting carriers of the mutant retinoblastoma allele. It is possible now to predict prenatally whether a child carries the retinoblastoma genome. This has enabled early detection of retinoblastoma and improved outcome. Also these children are at risk for mesenchymal tumors in early adult life necessitating life long vigilance. Great strides have been made in the management of retinoblastoma. Introduction of a new pathological staging system and addition of combination chemotherapy for extraocular disease has led to more than 80% long term disease free survivors in this group of patients, who earlier had a very poor outcome. For localized intraocular disease, local treatment seems to be all that is necessary. Newer radiation techniques have helped preserve useful vision and reduced radiation related side effects.

Morphological studies on the larval stages of three species of Setaria and Dirofilaria repens.

This paper reports for the first time the morphology of larval stages of Setaria labiato-papillosa. The infective larvae of this species had two circles of small papillae on the cephalic end, 4 papillae for outer circle and 6 for inner circle. The caudal end of S. labiato-papillosa is in digital form with 3 transversally arranged papillae. There are 2 circles of small papillae on the cephalic end of S. leichungwingi and S. equina, 4 for each circle; the caudal terminal of the former species is willow-shaped with 3 pearl-like papillae, and that of the latter is conical shaped with 1 bulbed papilla, 2 slightly protruded papillae at sub-terminal. The anal ratios of all the above 3 species are below 3. Morphology of larval stages of Dirofilaria repens was also primarily described in China. The 3 bulbed caudal papillae of the infective larvae are closely arranged, and the anal ratio being less than 2. A key to infective larvae of 8 species of filaria was worked out according to relevant literature and the present study.