Clinical characteristics of unvaccinated or incompletely vaccinated children with neurological manifestations due to SARS-CoV-2 Omicron infection.

Omicron generally causes milder disease than previous strains of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), especially in fully vaccinated individuals. However, incompletely vaccinated children may develop Omicron-related complications such as those affecting the central nervous system. To characterize the spectrum of clinical manifestations of neuro-COVID and to identify potential biomarkers associated with clinical outcomes, we recruited 15 children hospitalized for Omicron-related neurological manifestations in three hospitals in Hong Kong (9 boys and 6 girls aged 1-13 years). All were unvaccinated or incompletely vaccinated. Fourteen (93.3%) were admitted for convulsion, including benign febrile seizure (n = 7), complex febrile seizure (n = 2), seizure with fever (n = 3), and recurrent breakthrough seizure (n = 2), and the remaining nonconvulsive patient developed encephalopathic state with impaired consciousness. None of the seven children with benign febrile seizure and six of eight children with other neurological manifestations had residual deficits at 9-month follow-up. SARS-CoV-2 RNA was undetectable in the cerebrospinal fluid (CSF) specimens of seven patients who underwent lumbar puncture. Spike-and-wave/sharp waves affecting the frontal lobes were detected in four of seven (57.1%) patients who underwent electroencephalogram. Children with Omicron-related neurological manifestations had significantly higher blood levels of IL-6 (p < 0.001) and CHI3L1 (p = 0.022) than healthy controls, and higher CSF levels of IL-6 (p = 0.002) than children with non-COVID-19-related febrile illnesses. Higher CSF-to-blood ratios of IL-8 and CHI3L1 were associated with longer length of stay, whereas higher ratios of IL-6 and IL-8 were associated with higher blood tau level. The role of CSF:blood ratio of IL-6, IL-8, and CHI3L1 as prognostic markers for neuro-COVID should be further evaluated.

Diazoxide-unresponsive Hyperinsulinemic Hypoglycaemia in a Preterm Infant with Heterozygous Insulin Receptor Gene Mutation.

Homozygous or compound heterozygous mutations in insulin receptor gene (INSR) lead to marked insulin resistance and hyperglycaemia in Donohue syndrome and Rabson-Mendenhall syndrome, conditions which are associated with significant morbidity early in life. On the other hand, heterozygous INSR gene mutations result in milder phenotype known as type A insulin resistance syndrome. While presentation in adults with this condition is well reported, phenotypes in infant are less well-characterized. We herein report an infant presenting with hyperinsulinemic hypoglycaemia who did not respond to diazoxide therapy. She was subsequently found to carry heterozygous INSR gene mutation. Our patient was a female infant born at 29 weeks of gestation who developed recurrent hypoglycaemia in early infancy. Workup showed hyperinsulinism and she was started on first-line therapy with diazoxide and high-calorie feeds. However, continuous blood glucose monitoring showed post-prandial hyperglycaemia followed by rapid fall to hypogylcaemia. Whole exome sequencing was performed to investigate for diazoxide-unresponsive hyperinsulinism, which revealed a likely pathogenic mutation in the INSR gene c.1246C>T p. (R416X). This nonsense mutation was inherited from the father. With the molecular diagnosis, diazoxide was stopped and she followed a diet with low glycaemic-index food. Subsequent monitoring showed stable glucose profile. Our case highlights the importance to consider type A insulin resistance syndrome when no mutation could be identified in the ABCC8/KCNJ11 genes in diazoxide-unresponsive hyperinsulinism. With autosomal dominant inheritance, cascade screening should be performed in family members to identify those harbouring the mutation as they are at risk of early onset diabetes.

Air dispersal of respiratory viruses other than severe acute respiratory coronavirus virus 2 (SARS-CoV-2) and the implication on hospital infection control.

BACKGROUND: Air dispersal of respiratory viruses other than SARS-CoV-2 has not been systematically reported. The incidence and factors associated with air dispersal of respiratory viruses are largely unknown. METHODS: We performed air sampling by collecting 72,000 L of air over 6 hours for pediatric and adolescent patients infected with parainfluenza virus 3 (PIF3), respiratory syncytial virus (RSV), rhinovirus, and adenovirus. The patients were singly or 2-patient cohort isolated in airborne infection isolation rooms (AIIRs) from December 3, 2021, to January 26, 2022. The viral load in nasopharyngeal aspirates (NPA) and air samples were measured. Factors associated with air dispersal were investigated and analyzed. RESULTS: Of 20 singly isolated patients with median age of 30 months (range, 3 months-15 years), 7 (35%) had air dispersal of the viruses compatible with their NPA results. These included 4 (40%) of 10 PIF3-infected patients, 2 (66%) of 3 RSV-infected patients, and 1 (50%) of 2 adenovirus-infected patients. The mean viral load in their room air sample was 1.58×103 copies/mL. Compared with 13 patients (65%) without air dispersal, these 7 patients had a significantly higher mean viral load in their NPA specimens (6.15×107 copies/mL vs 1.61×105 copies/mL; P < .001). Another 14 patients were placed in cohorts as 7 pairs infected with the same virus (PIF3, 2 pairs; RSV, 3 pairs; rhinovirus, 1 pair; and adenovirus, 1 pair) in double-bed AIIRs, all of which had air dispersal. The mean room air viral load in 2-patient cohorts was significantly higher than in rooms of singly isolated patients (1.02×104 copies/mL vs 1.58×103 copies/mL; P = .020). CONCLUSION: Air dispersal of common respiratory viruses may have infection prevention and public health implications.

Rebounds, regresses, and recovery: A 15-year study of the coral reef community at Pila'a, Kaua'i after decades of natural and anthropogenic stress events.

Pila'a reef on the north shore of Kaua'i, Hawai'i was subjected to a major flood event in 2001 that deposited extensive sediment on the reef flat, resulting in high coral mortality. To document potential recovery, this study replicated benthic and sediment surveys conducted immediately following the event and 15 years later. Coral cores were analyzed to determine coral growth rates and density. Our results suggest that significant reduction in terrigenous sediments has led to partial ecosystem recovery based on coral species and colony increases, more balanced size frequency distributions, improved coral condition, and enhanced coral recruitment despite lack of recovery of large dead coral colonies. However, within this 15-year period, episodic storms and a bleaching event impeded the recovery process, preventing full recovery and continuously threatening the coral reef community. As climate change progresses, the intensity and frequency of these disturbances are predicted to increase.

Who should return for an oral glucose tolerance test? A proposed clinical pathway based on retrospective analysis of 332 children.

OBJECTIVES: Fasting plasma glucose or oral glucose tolerance test (OGTT) is the traditional diagnostic tool for type 2 diabetes (T2DM). However, fasting is required and implementation in all overweight/obese subjects is not practical. This study aimed to formulate a clinical pathway to stratify subjects according to their risk of abnormal OGTT. METHODS: This retrospective study included patients with overweight or obesity who had undergone OGTT in a tertiary paediatric unit from 2012 to 2018. The optimal haemoglobin A1c (HbA1c) cutoff that predicts abnormal OGTT was evaluated. Other non-fasting parameters, in combination with this HbA1c cutoff, were also explored as predictors of abnormal OGTT. RESULTS: Three hundred and thirty-two patients (boys: 54.2%, Chinese: 97.3%) were included for analysis, of which, 272 (81.9%) patients had normal OGTT while 60 (18.0%) patients had abnormal OGTT (prediabetes or T2DM). Optimal HbA1c predicting abnormal OGTT was 5.5% (AUC 0.71; sensitivity of 66.7% and specificity of 71%). When HbA1c≥5.5% was combined with positive family history and abnormal alanine transaminase (ALT) level, the positive predictive value for abnormal OGTT was increased from 33.6 to 61.6%. CONCLUSIONS: HbA1c, family history of T2DM and ALT level could be used to derive a clinical pathway to stratify children who have high risk of abnormal OGTT.

Primary varicella zoster infection compared to varicella vaccine reactivation associated meningitis in immunocompetent children.

We diagnosed varicella zoster virus (VZV) meningitis in a healthy adolescent boy who presented without a rash or fever. We aim to compare VZV reactivation meningitis in children after primary VZV infection and VZV vaccination. We reviewed the literature up until June 2020 using Pubmed/MEDLINE and EMBASE databases using 'varicella zoster', 'meningitis' and 'children' as keywords. Only English articles were included. Twenty-five cases were included in this review. Children who had VZV reactivation meningitis after vaccination were younger (7 ± 3.4 years vs. 11.9 ± 3.6 years, P = 0.0038), had a shorter interval between first exposure to reactivation (5.6 ± 2.9 years vs. 8.8 ± 3.2 years, P = 0.018) and more likely to have a rash (100% vs. 55%, P = 0.04). VZV reactivation meningitis occurs after both primary VZV infection and VZV vaccination. The absence of exanthem, fever or meningism does not rule out VZV meningitis.

Headache in a Child with Pseudohypoparathyroidism: An Alarming Symptom Not to Miss.

BACKGROUND: While the endocrine manifestations of pseudohypoparathyroidism are well known, less is known about the associated brain and spine abnormalities. These abnormalities may present with nonspecific symptoms in the paediatric population, and lack of awareness to these uncommon manifestations of the disease may result in a delay in necessary intervention. Case Presentation. We herein present a case of known pseudohypoparathyroidism type 1a who presented initially with minor head injury. She later developed progressive worsening headache, increased irritability, and vomiting. Repeated imaging showed hydrocephalus and Chiari malformation type 1 necessitating emergency craniectomy. CONCLUSION: Growth hormone deficiency, a common manifestation of pseudohypoparathyroidism type 1a, results in underdevelopment of the posterior cranial fossa and may account for the higher incidence of Chiari malformation in this group of patients. Other associated neurological features reported in pseudohypoparathyroidism type 1a include spinal stenosis, syringomyelia, and craniosynostosis. While less commonly seen, awareness to these associations is important in order to optimize the multidisciplinary care to this group of patients.

Isoniazid-induced gynaecomastia: report of a paediatric case and review of literature.

BACKGROUND: Gynaecomastia is a fairly common condition in puberty but is rare in prepubertal boys. While it is necessary to exclude possible endocrinopathay in prepubertal gynaecomastia, medication is an important and potentially reversible cause to consider in new onset gynaecomastia. Isoniazid-induced gynaecomastia has been reported in adult males, but none was reported in the paediatric population and general paediatricians may not be aware of this uncommon side effect. CASE PRESENTATION: We hereby report a 11-year-old prepubertal boy who developed gynaecomastia while taking anti-tuberculosis drugs. Investigations excluded endocrinopathies. Gynaecomastia subsided 8 weeks after stopping isoniazid. CONCLUSION: This case is the first paediatric case report describing the association of gynaecomastia with isoniazid use. It is important for general paediatricians to recognize this entity, as prompt diagnosis and cessation of the offending drug can lead to resolution of the problem.

Catheter-Based Splanchnic Denervation for Treatment of Hypertensive Cardiomyopathy.

Emerging preclinical data suggest that splanchnic sympathetic nerve activation may play an important role in the pathophysiology of hypertension. We sought to determine the potential therapeutic application of catheter-based splanchnic denervation in a clinically relevant large animal model of hypertensive cardiomyopathy (hCMP). Sustained elevated blood pressure was induced in adult pigs using a combination of intravenous infusion of Ang II (angiotensin II) and subcutaneous implantation of deoxycorticosterone acetate pellets to establish a large animal model of hCMP. Serial changes in cardiac echocardiographic and invasive hemodynamic parameters and neurohumoral biomarkers were investigated in animals with hypertension alone (n=9) and hypertension with catheter-based splanchnic denervation (n=6). Another 6 pigs without hypertension induction served as controls. At 10 weeks, hypertensive animals developed sustained elevated blood pressure and phenotype of hCMP with significant systolic and diastolic dysfunction, and left ventricular remodeling and hypertrophy as determined by invasive hemodynamic and echocardiogram assessments, respectively, and increased venoarterial norepinephrine gradient over the myocardium, kidneys, and splanchnic organs compared with baseline. Catheter-based splanchnic denervation decreased the venoarterial norepinephrine gradient over the splanchnic organs associated with the reduced splenic sympathetic nerve innervation; attenuated the elevated blood pressure, left ventricular remodeling, and hypertrophy; and preserved left ventricular systolic and diastolic function at 20 weeks in pigs with hCMP. Our results provide novel mechanistic insight into the role of splenic sympathetic nerve innervation in hypertension and important proof-of-principle data for the therapeutic application of catheter-based splanchnic denervation in a large animal model of hCMP.

Evidence of acclimatization or adaptation in Hawaiian corals to higher ocean temperatures.

Ocean temperatures have been accelerating at an alarming rate mainly due to anthropogenic fossil fuel emissions. This has led to an increase in the severity and duration of coral bleaching events. Predicted projections for the state of reefs do not take into account the rates of adaptation or acclimatization of corals as these have not as yet been fully documented. To determine any possible changes in thermal tolerances, manipulative experiments were conducted to precisely replicate the initial, pivotal research defining threshold temperatures of corals nearly five decades ago. Statistically higher calcification rates, survivorship, and lower mortality were observed in Montipora capitata, Pocillopora damicornis, and Lobactis scutaria in the present study at 31 °C compared to the original 1970 findings. First whole colony mortality was also observed to occur sooner in 1970 than in 2017 in M. capitata (3 d vs. 15 d respectively), L. scutaria (3 d vs. 17 d), and in P. damicornis (3 d vs. 13 d). Additionally, bleaching occurred sooner in 1970 compared to the 2017 experiment across species. Irradiance was an important factor during the recovery period for mortality but did not significantly alter calcification. Mortality was decreased by 17% with a 50% reduction in irradiance during the recovery period. These findings provide the first evidence of coral acclimatization or adaptation to increasing ocean temperatures for corals collected from the same location and using close replication of the experiment conducted nearly 50 years earlier. An important factor in this increased resistance to elevated temperature may be related to removal of the discharge of treated sewage into Kane'ohe Bay and resulting decrease in nitrification and eutrophication. However, this level of increased temperature tolerance may not be occurring rapidly enough to escape the projected increased intensity of bleaching events, as evidenced by the recent 2014 and 2015 high coral mortality in Hawai'i (34%) and in the tropics worldwide.

Linking Healthcare and Social Service Databases to Study the Epidemiology of Child Maltreatment and Associated Health Problems: Hong Kong's Experience.

OBJECTIVE: To examine the incidence and trend of child maltreatment and its associated health problems in Hong Kong by linking healthcare and social service databases. STUDY DESIGN: Data on 4816 children under the age of 18 years registered with the Child Protection Registry and matching health records in public hospitals in Hong Kong from 2003 to 2010 were extracted. Associations were examined between different types of child maltreatment and child's medical diagnosis according to the International Statistical Classification of Diseases and Related Health Problems, 10th Revision codes including suicidal attempt (X60-X84), nonchild maltreatment related injuries (S00-S99; T00-T98, excluding T74 and T76 that are maltreatment related injuries), mental health problems (F00-F99), and congenital malformations/chromosomal abnormalities (Q00-Q99). RESULTS: Significant rising trends were found for child physical abuse, neglect, and sexual abuse during the period from 2003 to 2010. Psychological abuse remained stable. Risk of suicide attempt was higher among children suffering from sexual abuse, psychological abuse, and children experiencing multiple abuses; mental health diagnoses were more common in victims of psychological and multiple abuses. Congenital malformations and chromosomal abnormalities were more commonly found among neglected children. CONCLUSIONS: In contrast to the decreasing trend observed in the West during the study period, there has been an escalating trend in child maltreatment in Hong Kong and child maltreatment is strongly associated with major health problems. This is one of the first studies to demonstrate the power of linking healthcare and social service databases, which allows for both a better understanding of the impact of child maltreatment and as a guide future policy and service planning.

Relationship of biomarkers of extracellular matrix with myocardial function in Type 2 diabetes mellitus.

AIM: The study evaluated the relationship of extracellular matrix and renin angiotensin system with myocardial dysfunction in Type 2 diabetes mellitus. METHODS: All patients underwent resting and exercise echocardiography, including conventional parameters, E/E' ratio, global longitudinal strain and diastolic function reserve index. Plasma matrix metalloproteinase-1, TIMP-1, amino-terminal propeptide of type I and type III procollagen and renin angiotensin system activity were measured. RESULTS: As patients with diastolic dysfunction had a higher plasma level of TIMP-1 and propeptide of type III procollagen than those with no diastolic dysfunction. After multivariate adjustment, TIMP-1 associated with E/E' (both at rest and stress) and diastolic function reserve index. CONCLUSION: TIMP-1 is independently associated with myocardial diastolic dysfunction in patients with Type 2 diabetes mellitus.

Risk factors for child physical abuse and neglect among Chinese young mothers.

Although studies have reported a linkage between young pregnancy and child maltreatment risk, it is still unclear about what factors place young mothers at greater risk of maltreating their child in Chinese context. Based on the socio-ecological model, risk factors in 4 domains: family background/structure, maternal stressors, mother-child interaction, and child behavioral issue in relation to physical assault, neglect, both physical assault and neglect, and either physical assault or neglect among Chinese young mothers in Hong Kong were assessed. 392 young mothers were recruited from an integrated supportive program for young mothers. The mean age of mothers at delivery was 21.8 (SD=3.0) and 52.3% were married. Individual risk factors and cumulative risk domains related to different child maltreatment groups were examined. Our results show both overlapping and unique risk factors across the domains associated with physical assault and neglect. Further, young families exposed to higher number of risk domains show higher rates for physical assault and neglect, co-occurrence of physical assault and neglect, and either form of maltreatment. In addition, various risk domains were found to be particularly important for different forms of maltreatment: family background/structure domain was found to be an important risk domain for neglect; mother-child interaction domain for both physical assault and neglect; family background/structure and maternal stressors domains for either physical assault or neglect. Closer examination of a subgroup of adolescent mothers aged 18 and below shows that family background/structure was an important risk domain for this group.

Improvement of Myocardial Function Following Catheter-Based Renal Denervation in Heart Failure.

Renal denervation (RD) is a potential novel nonpharmacological therapy for heart failure (HF). We performed bilateral catheter-based RD in 10 adult pigs and compared them with 10 control subjects after induction of HF to investigate the long-term beneficial effects of RD on left ventricular (LV) function and regional norepinephrine gradient after conventional HF pharmacological therapy. Compared with control subjects, animals treated with RD demonstrated an improvement in LV function and reduction of norepinephrine gradients over the myocardium and kidney at 10-week follow-up. Our results demonstrated that effective bilateral RD decrease regional norepinephrine gradients and improve LV contractile function compared with medical therapy alone.

Effectiveness of a culturally attuned Internet-based depression prevention program for Chinese adolescents: A randomized controlled trial.

BACKGROUND: Depression prevention among adolescents is crucial for reducing the global disease burden. Internet-based depression prevention approaches are found to be effective but they were mostly evaluated in a Western context. Grasping the Opportunity is a Chinese Internet intervention, which was translated and modified from CATCH-IT developed in the West. We aimed to evaluate the effectiveness of Grasp the Opportunity in reducing depressive symptoms in Chinese adolescents. METHODS: In this randomized controlled trial, Chinese adolescents aged 13 to 17 years with mild-to-moderate depressive symptoms were recruited from three secondary schools in Hong Kong. The participants (n = 257) were randomly assigned to receive either intervention or attention control. The primary outcome was the improvement in depressive symptoms according to the revised Center for Epidemiologic Studies Depression Scale (CESD-R) at the 12-month follow-up. Analyses were performed using intention to treat (ITT). RESULTS: The participants were randomly assigned to receive the intervention (n = 130) or attention control (n = 127). Follow-up data were obtained from 250 (97%) participants. Only 26 (10%) participants completed the intervention. Compared to the attention control, Grasp the Opportunity led to reductions in depressive symptoms at the 12-month follow-up with a medium effect size using ITT analysis (mean difference 2.6, 95% CI 0.59-5.55, effect size d = 0.36). CONCLUSIONS: Grasp the Opportunity is effective in reducing depressive symptoms in Chinese adolescents over a long follow-up period. Poor completion rate is the major challenge in the study.

Adaptation of an internet-based depression prevention intervention for Chinese adolescents: from "CATCH-IT" to "grasp the opportunity".

BACKGROUND: There is a dearth of information on the compatibility of Western-developed, internet-based interventions that prevent onset and precipitation of depression in global settings. Recently, Project CATCH-IT (Competent Adulthood Transition with Cognitive-behavioral, Humanistic and Interpersonal Training), an information technology-based intervention, was adapted to prevent depression in Hong Kong Chinese adolescents. This paper evaluates qualitative data from consultations to develop a revised intervention of CATCH-IT for Hong Kong youth. METHODS: A theoretical thematic analysis approach was used to analyze data. Materials from three consultation trips which included focus groups (2007), an expert panel (2007), a public health campaign (2009), and a joint primary care physician-social worker review group (2010) were compiled. Authors (KS and AZ) independently reviewed the data and applied the theoretical framework of behavioral vaccines to code the data. These data were subsequently consolidated to provide a coherent narrative analysis. RESULTS: The cognitive behavioral therapy (CBT), behavioral activation (BA), and resiliency modules were maintained, while the interpersonal therapy (IPT) modules of CATCH-IT were excluded in the Hong Kong adaptation. Concurrent self-reports of drinking, smoking, illicit drug use and gambling behavior were added. Rather than primary care consultations, social worker consultations may be the best point of entry for intervention. CONCLUSION: Socio-cultural relevance of psychotherapeutics and delivery context of internet-based interventions will require significant adaptation for the Hong Kong setting. However, because of community engagement throughout the process of adaptation, we believe the CATCH-IT intervention can be adapted for Chinese adolescents in Hong Kong with retained fidelity. The revised intervention is called "Grasp the Opportunity".

Smad7 transgene attenuates peritoneal fibrosis in uremic rats treated with peritoneal dialysis.

Transforming growth factor beta (TGF-beta) plays a critical role in the pathogenesis of the peritoneal fibrosis that complicates long-term peritoneal dialysis (PD). We studied the TGF-beta/Smad signaling pathway in peritoneal fibrosis induced in uremic rats treated with PD and explored the therapeutic potential of Smad7 to prevent fibrogenesis. After subtotal nephrectomy, uremic rats were treated with peritoneal dialysis using 4.25% dextrose-containing fluid. The peritoneum of uremic rats treated with PD demonstrated fibrosis, increased TGF-beta expression, increased Smad2/3 activation, decreased Smad7 expression, and increased expression of fibrogenic and angiogenic factors. In addition, peritoneal function was impaired and its structure was altered, including a thickened submesothelial layer. In rats transfected with a Smad7 transgene using an ultrasound-microbubble-mediated system, peritoneal fibrosis was attenuated, peritoneal function was improved, and Smad2/3 activation was inhibited. We suggest that administration of Smad7 inhibits peritoneal fibrogenesis in uremic rats treated with PD by correcting the imbalance between downregulated Smad7 and activated Smad2/3. Blockade of the TGF-beta/Smad signaling pathway may represent a novel therapeutic approach to prevent peritoneal fibrosis in patients treated with PD.

Activation of tubular epithelial cells in diabetic nephropathy and the role of the peroxisome proliferator-activated receptor-gamma agonist.

The effects of advanced glycation end products (AGE) in the form of glycated albumin (GA) on the proinflammatory phenotype of cultured renal proximal tubular epithelial cells (PTEC) and the therapeutic potential of the peroxisome proliferator-activated receptor-gamma (PPAR-gamma) agonist were studied. Human PTEC were exposed to medium alone or supplemented with albumin or GA with or without previous addition of rosiglitazone (0.1 to 0.5 microM). Exposure to GA (up to 0.5 mg/ml) but not the equivalent dose of neat albumin significantly upregulated both mRNA and protein expression of IL-8 and soluble intercellular adhesion molecule-1 (sICAM-1) in a dose- and time-dependent manner. Using immunohistochemistry, ICAM-1 signals were detected in the tubular epithelia and peritubular capillaries in association with AGE deposition and leukocyte infiltration, whereas IL-8 staining was localized in the tubular epithelia of human diabetic kidney biopsies. Also in a dose-dependent manner, GA (0.5 mg/ml) but not albumin caused nuclear translocation of NF-kappaB and activation of mitogen-activated protein kinase (MAPK) p44/p42 and signal transducer and activator of transcription (STAT-1). Inhibition of these pathways with pyrrolidine dithiocarbamate, PD 98059, and fludarabine, respectively, attenuated GA-induced IL-8 secretion. Rosiglitazone dose-dependently attenuated GA-induced IL-8 and ICAM-1 signals in PTEC and completely abolished GA-induced STAT-1 signals but had no effect on NF-kappaB and MAPK activation. These findings suggest that AGE stimulate renal tubular expression of adhesion molecule and chemokine that together may account for the transmigration of inflammatory cells into the interstitial space during diabetic tubulopathy. Such proinflammatory phenotype may be partially modified by PPAR-gamma ligation through STAT-1 inhibition independent of NF-kappaB transcriptional activity and MAPK signaling.

The study of Chinese medicinal herbal formula Shen San Fang in the treatment of experimental IgA nephropathy.

IgA nephropathy (IgAN) is the most common primary glomerulonephritis worldwide, yet there is no effective or specific therapy. Shen San Fang (S3F) is a traditional Chinese herbal medicinal formula that has been used in China for many years to treat patients with hematuria. The aim of this study is to test the therapeutic value of S3F in an experimental model of IgAN. IgAN was induced in Lewis rats by continuous oral immunization with bovine gamma-globulin (BGG) in the drinking water for 8 weeks, followed by intravenous injection of 1 mg BGG daily for 3 successive days. The rats were randomly divided into four groups (five rats/group): control, control receiving S3F, induction of IgAN, and IgAN receiving S3E S3F decoction was fed to rats beginning week 4 from the first day of oral sensitization with BGG. The S3F treatment was continued until the rats were sacrificed or for a 4-week period. Hematuria, renal immunohistochemistry for IgA and transforming growth factor-beta 1 (TGF-beta1), renal histopathology, and renal content of TGF-beta1 were measured. Rats developing IgAN had marked hematuria, profound mesangial proliferation and mesangial expansion, intense and diffuse glomerular IgA deposition, increased glomerular TGF-beta1 expression, and raised renal TGF-beta1 levels. S3F treatment resulted in a significant reduction of hematuria, decreased mesangial IgA deposition, weaker immunostaining of TGF-beta1 in glomerulus, and a lower renal TGF-beta1 concentration. Our animal data suggests a therapeutic value for the Chinese medicinal formula S3F in experimental IgAN. This beneficial effect was due to reduced glomerular IgA deposition and TGF-beta1 expression. Our preliminary findings hold promise for future human therapy.