Nonylphenol releases arachidonic acid in rat Sertoli cells via activation of PKA and PLA2.

In brief: The endocrine disruptor, nonylphenol (NP) increases 20:4n-6 release in Sertoli cells via PKA/cPLA2 activation. Our data show that lipid metabolism could be a target of NP-induced abnormal reproductive outcomes. Abstract: Nonylphenol (NP), an endocrine-disrupting chemical, is an environmental contaminant, and many notorious effects on male fertility have been reported in animal models and wild-type species. Here, we evaluated the effects of NP in follicle-stimulating hormone (FSH) signal transduction pathways and lipid metabolism using an in vitro model of rat Sertoli cell (SC) primary culture. Results show that an acute (1 h) SC exposure to NP (10 µM) increased the intra- and extra-cellular concentrations of free fatty acids (FFAs), mainly arachidonic acid (20:4n-6). Phosphatidylinositol seemed to be the major phospholipid source of this 20:4n-6 release by activation of the protein kinase A (PKA)/cytoplasmic phospholipase A2 (cPLA2) pathway. NP also increased diacylglycerols (DAG) levels and the expression (mRNA) of cyclooxygenase 2 (Cox2) and prostaglandin E2 (PGE2) levels. It is noteworthy that accumulation of lipid droplets took place after 24 h NP exposition, which was prevented by both a PKA inhibitor and a PLA2 inhibitor. Like FSH, NP triggers the release of 20:4n-6, which is a substrate for PGE2 synthesis via PKA/PLA2 activation. In addition, NP induces the formation of DAG, which could be required as a cofactor of the PKC-mediated activation of the COX2 inflammatory pathway. Our findings suggest that NP alters lipid homeostasis in SCs by inducing the activation of pro-inflammatory pathways that may trigger adverse effects in testis physiology over time. Concomitantly, the SC enhances the acylation of surplus FFAs (including 20:4n-6) in neutral lipids as a protective mechanism to shield itself from lipotoxicity and pro-inflammatory signals.

Mitochondrial Transfer as a Novel Therapeutic Approach in Disease Diagnosis and Treatment.

Mitochondrial dysfunction is a hallmark of numerous diseases, including neurodegenerative disorders, metabolic disorders, and cancer. Mitochondrial transfer, the transfer of mitochondria from one cell to another, has recently emerged as a potential therapeutic approach for restoring mitochondrial function in diseased cells. In this review, we summarize the current understanding of mitochondrial transfer, including its mechanisms, potential therapeutic applications, and impact on cell death pathways. We also discuss the future directions and challenges in the field of mitochondrial transfer as a novel therapeutic approach in disease diagnosis and treatment.

New Insights and Potential Therapeutic Interventions in Metabolic Diseases.

Endocrine homeostasis and metabolic diseases have been the subject of extensive research in recent years. The development of new techniques and insights has led to a deeper understanding of the mechanisms underlying these conditions and opened up new avenues for diagnosis and treatment. In this review, we discussed the rise of metabolic diseases, especially in Western countries, the genetical, psychological, and behavioral basis of metabolic diseases, the role of nutrition and physical activity in the development of metabolic diseases, the role of single-cell transcriptomics, gut microbiota, epigenetics, advanced imaging techniques, and cell-based therapies in metabolic diseases. Finally, practical applications derived from this information are made.

[Post-obstructive polyuria. Pathophysiological analysis of a case]. / Poliuria post-obstructiva. Análisis fisiopatológico de un caso.

The relief of the impediment to urinary flow is the treatment of acute kidney failure due to urinary tract obstruction. However, there is a risk of inducing massive polyuria, which can be self-limited or produce severe contraction of the intravascular volume with pre-renal acute kidney failure and alterations in the internal environment. Polyuria, urine output > 3 L/d or > 200 mL/min for more than 2 hours, can have multiple causes, and can be classified as osmotic, aqueous or mixed. Post-obstructive polyuria obeys different pathogenic mechanisms, which overlap and vary during a patient's evolution. Initially, there is a decrease in vasoconstrictor factors and an increase in renal blood flow, which, added to the excess of urea accumulated, will cause intense osmotic diuresis (osmotic polyuria due to urea). Added to these factors are the positive sodium and water balance during acute renal failure, plus the contributions of crystalloid solutions to replace diuresis (ionic osmotic polyuria). Finally, there may be tubular dysfunction and decreased solutes in the renal medullary interstitium, adding resistance to the action of vasopressin. The latter causes a loss of free water (mixed polyuria). We present the case of a patient with post-obstructive polyuria where, by analyzing the clinical symptoms and laboratory alterations, it was possible to interpret the mechanisms of polyuria and administer appropriate treatment for the pathogenic mechanism.

[Severe metabolic disorder associated with an enterovesical fistula. Report of one case]. / Trastorno grave del medio interno por fístula enterovesical, a propósito de un caso clínico.

Enterovesical fistula (EVF) is a fistulous communication between the intestine and the bladder. It is uncommon and its classic clinical manifestations are the presence of pneumaturia, fecaluria, suprapubic pain and recurrent urinary infections. Surgical repair of EVF leads to rapid correction of both diarrhea and metabolic abnormalities. We report a 73-year-old diabetic woman with a neurogenic bladder secondary to a spine meningioma. She presented with diarrhea, vomiting, impaired consciousness and metabolic acidosis. She developed hypernatremia, hypokalemia, hypocalcemia, and hypophosphatemia, which were successfully corrected.

[Intravenous sodium bicarbonate. When, how and why to use it?] / Bicarbonato de sodio intravenoso ¿Cuándo, cómo y por qué utilizarlo?

Severe metabolic acidosis is defined by a pH < 7.2 with HCO3- < 8 mE- q/L in plasma. Its best treatment is to correct the underlying cause. However, acidemia produces multiple complications such as resistance to the action of catecholamines, pulmonary vasoconstriction, impaired cardiovascular function, hyperkalemia, immunological dysregulation, respiratory muscle fatigue, neurological impairment, cellular dysfunction, and finally, it contributes to multisystemic failure. Intravenous NaHCO3 buffers severe acidemia, preventing the associated damage and gains time while the causal disease is corrected. Its indication requires a risk-benefit assessment, considering its complications. These are hypernatremia, hypokalemia, ionic hypocalcemia, rebound alkalosis, and intracellular acidosis. For this reason, therapy must be "adapted" and administered judiciously. The patient will require monitoring with serial evaluation of the internal environment, especially arterial blood gases, plasma electrolytes, and ionized calcium. Isotonic solutions should be preferred instead of hypertonic bicarbonate. The development of hypernatremia must be prevented, calcium must be provided for hypocalcemia to improve cardiovascular function. Furthermore, in mechanically ventilated patients, a respiratory response similar to the one that would develop physiologically, must be established to be able to extract excess CO2 and thus avoid intracellular acidosis. It is possible to estimate the bicarbonate deficit, speed, and volume of its infusion. However, the calculations are only for reference. More important is to start intravenous NaHCO3 when needed, administer it judiciously, manage its side effects, and continue it to a safe goal. In this review we address all the necessary elements to consider in the administration of intravenous NaHCO3, highlighting why it is the best buffer for the management of severe metabolic acidosis.

[Severe respiratory alkalosis due to psychogenic hyperventilation. Report of one case]. / Alcalosis respiratoria grave, la transformación de un cuadro funcional en orgánico. Caso clínico.

Severe respiratory alkalosis is a life-threatening condition, as it induces hypo- calcaemia and extreme adrenergic sensitivity leading to cerebral and myocardial vasoconstriction. We report a 37-year-old woman with previous consultations for a conversion disorder. While she was infected with SARS-CoV-2 (without pulmonary involvement), she consulted in the emergency room due to panic attacks. On admission, she developed a new conversion crisis with progressive clinical deterioration, hyperventilation, and severe respiratory alkalosis (pH 7.68, Bicarbonate 11.8 mEq/L and PaCO2 10 mmHg). Clinically, she was in a coma, with respiratory and heart rates 55 and 180 per min, a blood pressure of 140/90 mmHg, impaired perfusion (generalized lividity, distal coldness, and severe skin mottling) and tetany. She also had electrocardiographic changes and high troponin levels suggestive of ischemia, and hyperlactatemia. She was managed in the hospital with intravenous benzodiazepines. The clinical and laboratory manifestations resolved quickly, without the need for invasive measures and without systemic repercussions.

Diagnosis of light chain cast nephropathy through immunostaining of the urine: Perfecting the "liquid biopsy".

Light chain (LC) cast nephropathy is the main cause of kidney injury and an important determinant of poor survival in patients with multiple myeloma (MM). It is usually suspected when an MM patient with elevated serum concentration of free LC presents kidney failure, but it often requires confirmation by kidney biopsy. We report the case of a 73-year-old woman who presented with fatigue, weight loss, and constipation. Laboratory exams revealed anemia, hypercalcemia, and kidney failure. Urine sediment analysis demonstrated irregular crystalline "waxy type" casts. With the hypothesis of LC cast nephropathy, immunostaining of the urine sediment was performed. The analysis revealed several rectangular and irregular casts with intense and bright stain for λ LCs only. A myelogram was performed, showing extensive occupation of the bone marrow by plasma cells; and immunofixation in urine and serum revealed monoclonal IgG-λ component, confirming the diagnosis of IgG-λ MM. This case highlights the potential utility of the urine sediment analysis and immuno-staining as a reliable non-invasive alternative method for diagnosis of cast nephropathy in patients with monoclonal gammopathies.

[Comparative performance of urinary creatinine excretion estimating equations]. / Desempeño comparativo de ecuaciones de estimación de excreción urinaria de creatinina.

BACKGROUND: 24-hour urine collection accuracy is generally evaluated based on the values of urine creatinine (UCr) excretion, usually using ranges adjusted by weight. UCr excretion depends on several factors. Equations to estimate UCr in 24-hour collection (UCr/24h) that consider these factors have been developed. However, these formulas have not been evaluated in a sample of Latinamerican origin. AIM: To evaluate the performance of the existing UCr/24 h estimation equations in a sample of Latinamerican origin. MATERIAL AND METHODS: 24-hour urine collections from 181 ambulatory patients were analyzed. Measured UCr/24h was compared with estimated UCr (eUCr) through the equations of Ix (CKD-EPI), Gerber-Mann, Goldwasser, Cockcroft-Gault, Rule, Walser, Kawasaki, Tanaka and Huidobro. Performance of the nine equations to estimate UCr/24h was evaluated with the Pearson correlation and Lin concordance coefficients, and Bland-Altman method. Bias, precision, and accuracy (percentage of collections within 30% of measured UCr or P30) were also calculated. RESULTS: Measured UCr/24h in the 181 patients was 1236 + 378 mg. Correlation coefficient (Pearson) of the eUCr/24h with the equations of Walser, Ix and Huidobro and the measured UCr/24h was strongly positive. Rule and Kawasaki equations had the lowest positive correlation coefficients. Bias was similar using the formulas of Walser, Goldwasser, Kawasaki, Ix and Huidobro. Walser, Ix, Huidobro, Cockcroft-Gault and Goldwasser equations had good accuracy (P30 > 85%), while Gerber-Mann, Tanaka, Rule and Kawasaki formulas had a P30 < 65%. CONCLUSIONS: Walser, Ix and Huidobro equations had the best performance to estimate UCr/24h excretion in a population of latinamerican origin.

[Shiga toxin-associated hemolytic uremic syndrome with hypocomplementemia. Report of one case]. / Síndrome hemolítico urémico asociado a toxina Shiga con hipocomplementemia en edad atípica. Caso clínico.

The Shiga toxin associated (Stx) hemolytic uremic syndrome (HUS) is an important cause of acute renal failure (ARF) and the most common cause of thrombotic microangiopathy (TMA) in pediatrics. Primary atypical HUS (aHUS) is a rare disease due to a genetic defect in the alternative complement pathway. Both diseases may share clinical and laboratory elements, making differential diagnosis difficult, such as the presence of diarrhea in aHUS or complement alterations in HUS-Stx. The treatment and prognosis of both diseases is completely different. We report a 15-year-old male with severe HUS. After a self-limited diarrheal syndrome, he had a severe TMA and ARF, requiring renal replacement therapy. An extensive etiological study was carried out, ruling out the main causes of TMA. Alterations in complement factors were observed. Finally, the diagnosis of HUS-Stx was established. The patient evolved favorably with recovery of renal function.

[A new equation to estimate daily natriuresis from parameters in plasma and spot urine sample in the Chilean population]. / Nueva ecuación para la estimación de la natriuresis diaria a partir de parámetros en plasma y orina aislada en población chilena.

BACKGROUND: Excessive sodium intake is associated with increased cardiovascular morbidity and mortality. Daily sodium intake is usually inferred from sodium excretion in a 24-hour urine collection, which is cumbersome and prone to errors. Different formulas have attempted to estimate 24-hour urinary sodium from a spot urine sample. Unfortunately, their concordances are insufficient and have not been tested in our population. AIM: To develop an equation to predict 24-hour urine sodium from parameters in plasma and spot urine samples. To validate the equation and compare it with other formulas in Chilean population. MATERIAL AND METHODS: Analysis of 24-hour urine collections, plasma sample and spot urine sample from 174 adult outpatients (81% females) with an estimated glomerular filtration rate (eGFR) ≥ 60 mL/min/1.73m2. These were collected between 2015 and 2019 using standardized methods and educating patients about the correct method to collect 24 h urine samples. In all these patients, creatinine and electrolytes were measured in plasma and urine. A new equation was developed using a multiple linear regression model. RESULTS: Twenty-four-hour urine sodium excretion was significantly correlated with age, weight, height, eGFR, plasma osmolarity, urine electrolytes and parameters obtained from spot urine sample, among others. The new equation had a linear correlation with 24-hour natriuresis of 0.91 and the concordance was 0.9. The predictive capacity of the new equation was better than the existing formulas. CONCLUSIONS: We developed a formula to accurately predict daily natriuresis in the Chilean population.

[Comparison of different methods to estimate glomerular filtration rate in older adults]. / ¿Son equivalentes los diferentes métodos para estimar la función renal en los adultos mayores?

BACKGROUND: Glomerular filtration rate (GFR) estimation in older adults using a creatinine clearance/24-hour (CrCl) or an equation based on serum creatinine, are often considered equivalent by clinicians. AIM: To compare GFR estimated (eGFR) with the available equations and measured CrCl in patients ≥ 70 years. A secondary aim was to know the differences in chronic kidney disease (CKD) classification, when using the different eGFR formulas. PATIENTS AND METHODS: In 144 patients aged 77 ± 5 years (58% men), CrCl was measured and GFR was estimated using MDRD, CKD-EPI, BIS-1 and FAS formulas. The eGFR and the stage of CKD were compared according to the different equations used. RESULTS: GFR estimated by MDRD and CKD-EPI equations was 7.8 and 8.4 mL/min/1.73 m2 lower than 24-hour ClCr, respectively. This difference was even greater using the BIS-1 and FAS equations. Twenty-four-hour CrCl classified 47.2% of the patients in a category of renal function > 60 mL/min/1.73 m2, while MDRD and CKD-EPI equations classified just over a third, and BIS-1 and FAS formulas around 20% of the patients. CONCLUSIONS: The practice of considering equivalent the GFR estimation using the creatinine-based equations with measured creatinine clearance in older adults should be reconsidered, because their results differ markedly.

[Acute kidney injury caused by rhabdomyolysis as a SARS-CoV-2 infection manifestation. Report of one case]. / Insuficiencia renal aguda secundaria a rabdomiolisis como manifestación de infección por SARS-CoV-2.

SARS-CoV-2 infection has a wide spectrum of clinical manifestations secondary to the impairment of different organs, including kidney. Rhabdomyolysis is produced by disintegration of striated muscle and the liberation of its contents to the extracellular fluid and bloodstream. This may produce hydro electrolytic disorders and acute kidney injury. We report a 35-year-old female with a history of SARS-CoV-2 infection who was hospitalized because of respiratory failure and developed renal failure. The etiologic study showed elevated total creatine kinase levels and a magnetic resonance imaging confirmed rhabdomyolysis. The patient required supportive treatment with vasoactive drugs, mechanic ventilation and kidney replacement therapy. She had a favorable evolution with resolution of respiratory failure and improvement of kidney function.

[Stress induced ketoacidosis in spinal muscular atrophy. Report of one case]. / Cetoacidosis por estrés: caso clínico en paciente con atrofia muscular espinal.

Spinal muscular atrophy is an uncommon cause of ketoacidosis, where there is a decrease in muscle mass, an abnormal metabolism of glucose and fatty acids, and changes in neuroendocrine function. These conditions favor the accumulation of keto acids and the development of metabolic acidosis. We report a 26-year-old female, with a history of spinal muscular atrophy type III, consulting for abdominal pain and vomiting lasting one week. She was admitted to the emergency service somnolent and poorly perfused. She had a pH of 6.98, HCO3- of 3.8 mmol/L, pCO2 of 16.4 mmHg, BE of -26 mmol/L, delta ratio of 1.05, anion gap of 31 mEq/L, creatinine of 0.37 mg/dL, sodium of 147 mEq/L, potassium of 3.7 mEq/L, chloride of 112 mEq/L, lactate of 1.2 mmol/L, glucose of 108 mg/dL, albumin of 4.2 g/dL, ketonemia +++, ketonuria +, measured plasma osmolality of 322 mOsm/kg, estimated osmolality of 314 mOsm/kg, toxilab negative, salicylate levels < 3 µg/mL, acetaminophen levels < 1.2 µg/mL. Intravenous hydration and bicarbonate were started, without satisfactory response. Interpreting the clinical picture as a ketoacidosis induced by stress in a patient with spinal muscular atrophy, it was handled with glucose, amino acids, vitamins and trace elements, with a favorable response.

[Survival analysis of patients starting hemodialysis in Chile between 2013 and 2019]. / Análisis de sobrevida en pacientes incidentes de hemodiálisis en Chile, 2013-2019.

BACKGROUND: Renal replacement therapies, especially hemodialysis (HD) in end-stage kidney disease, avoid an inevitable death caused by the disease. However, in elderly patients with multiple comorbidities, this therapy could derive in a comparable survival than conservative management. Considering that HD represents a high cost for the health system, it is worth analyzing the effects of HD on survival. AIM: To analyze the survival and mortality of all national health security system's patients (FONASA) admitted to HD in Chile from 2013 to 2019. MATERIAL AND METHODS: We requested to the Ministry of Health information about all patients affiliated to the public health insurance system that started dialysis between 2013 and 2019. We evaluated the influence of age when starting HD, sex, presence of hypertension, presence of diabetes mellitus (DM), the region of residence, and year of admission on mortality. RESULTS: A total of 24,113 patients aged 61 ± 15 years (45% women) were analyzed. Forty five percent of patients were aged > 65 years. After 5 years of follow-up, the median survival in this age group was 36.1 months. Among patients who started HD at age > 85 years, the median survival was 14.8 months. Diabetic patients had a median survival of 52.3 months. Advanced age and DM were associated with higher annual mortality. Also, the region of residence and year of admission were associated with higher mortality at 3 and 12 months. CONCLUSIONS: The median survival of patients on HD is dependent on age and the presence of comorbidities, among other factors. We performed an analysis to determine if starting HD in older patients with comorbidities has a real benefit over conservative management in terms of survival.

[Methemoglobinemia caused by dapsone. Report of one case]. / Metahemoglobinemia, una entidad de diagnóstico complejo. Reporte de un caso.

Methemoglobinemia is a rare condition with serious consequences if not diagnosed. We report the case of a 64-year-old woman with a history of allergy to sulfa drugs and a recent diagnosis of a small vessel vasculitis (ANCA-p) who started induction therapy with corticosteroids and rituximab. Due to the need for infectious prophylaxis, and considering her history, dapsone was administered instead of cotrimoxazole after ruling out glucose-6-phosphate dehydrogenase deficiency. During the admission to the hospital for her second dose of rituximab, and while being asymptomatic, she persistently presented a pulse oximetry ≪ 90% despite the administration of O2. Therefore, the infusion was postponed to study the patient. The arterial gasometric study by direct potentiometry revealed an O2 saturation of 98%, with a saturation gap > 5%. Considering the use of dapsone, a methemoglobinemia was suspected and confirmed by co-oximetry (methemoglobinemia 9%). Dapsone was suspended and one week later, her methemoglobinemia was absent.

[A new equation to predict urine creatinine values using data from Chilean population]. / Nueva fórmula para estimar creatininuria en población chilena.

BACKGROUND: Evaluation of 24-hour collection accuracy is based on urinary creatinine excretion (UCr), usually using wide ranges indexed by weight. Equations that predict the expected UCr are also available. AIM: To generate an equation for estimating UCr in Chilean population and evaluate its performance in comparison to existing formulas. MATERIAL AND METHODS: A total of 464 24-hour urine collections from outpatients aged between 15 and 88 years old were used. Ninety percent of collections (n = 418) were randomly extracted to assess the association between absolute UCr values with sex, age, height and weight of participants. A formula was created to estimate the 24-hour UCr using a multiple linear regression model. In the remaining 10% of urine collections (n = 46), the performance of this formula and others reported in the literature were tested. RESULTS: Age, sex and weight were significantly associated with 24-hour UCr values. The new equation was able to predict UCr values with a similar accuracy than CKD-EPI and Walser equations and outperformed other equations. CONCLUSIONS: Our equation developed with Chilean values predicts 24-hour UCr values accurately.

[Paraprotein-related kidney disease. Experience in 22 cases]. / Nefropatías secundarias a paraproteína: perfil clínico a partir de hallazgos histológicos.

BACKGROUND: One of the devastating consequences of monoclonal gammopathies is the development of end-stage kidney disease, which can be prevented with an early diagnosis. Renal involvement can be secondary to saturation of paraproteins with intratubular precipitation or the glomerular deposition of paraproteins with secondary inflammation and destruction. These conditions can also be associated with monoclonal gammopathies that do not meet hematological treatment criteria, called monoclonal gammopathies of renal significance (MGRS). AIM: To report a retrospective analysis of patients who underwent a renal biopsy and whose final diagnosis was a form of monoclonal gammopathy. MATERIAL AND METHODS: We reviewed the clinical and laboratory features and response to treatment of 22 patients aged 63 ± 12 years (55% women) with a pathological diagnosis of a nephropathy associated with paraproteinemia. RESULTS: The most common hematological diagnosis was amyloidosis in 50% of patients, followed by cast nephropathy. The predominant clinical presentations were proteinuria (without nephrotic syndrome) and nephritic syndrome. Classic criteria such as erythrocyte sedimentation rate > 100 mm/h and protein-albumin gap were unusual. Serum light chain quantification was the test with the best yield to detect paraproteins. CONCLUSIONS: In this group of patients, light chains tend to affect the kidney more commonly than heavy chains. The prognosis of multiple myeloma is much worse than MGRS.

Intoxicación por etilenglicol, fisiopatología y enfrentamiento clínico.

Toxic alcohols can produce severe poisoning with multiple organic involvement and even death. The most common form is ethylene glycol. The diagnosis can be extremely difficult if there is no history of its consumption. Its clinical presentation can simulate other conditions. Ethylene glycol poisoning is characterized by an initial rise in plasma osmolal gap that decreases during the evolution, while alcohol is metabolized to acids. This last condition causes a metabolic acidosis with elevated anion gap. The clinical manifestations are diffuse neurological involvement initially, followed by hemodynamic alterations due to myocardial damage associated with hypocalcemia and acidemia. Subsequently, severe tubular renal damage appears, which may require renal replacement therapy, and finally, focal neurological alterations. To treat this poisoning, it is necessary to inhibit the transformation of alcohol into acids, increase the metabolism of the latter or withdraw them directly with hemodialysis.

Predictive Model for Response Rate to Narrowband Ultraviolet B Phototherapy in Vitiligo: A Retrospective Cohort Study of 579 Patients.

Vitiligo is an acquired depigmenting disorder. To date, there is no predictive model for its response rate to narrowband ultraviolet B (NBUVB) phototherapy. The aim of this study was to investigate the different types of response of patients with non-segmental vitiligo undergoing NBUVB 3 times a week. Many patients who were previously considered non-responders were given the opportunity to continue the treatment. Long-term maintenance of treatment and follow-up of a cohort of 579 patients enabled different subtypes of response (very rapid, rapid, average, slow and "non-responders") to be described for the first time, and a predictive model of response to be constructed based on repigmentation rate in the first 48 sessions of NBUVB. Among those patients who did not respond during the first 48 sessions, a new subgroup of patients was found, termed "very-slow" responders, who achieved a low, but significant, level of repigmentation after 96 sessions of NBUVB.