Neonatal AKI: An update.

Neonatal acute kidney injury (AKI) is a common complication, especially in the neonatal intensive care unit, that is associated with long term consequences and poor outcomes. Early detection and treatment is critical. Currently, neonatal AKI is defined with urinary markers and serum creatinine, with limitations on early detection and individual treatment. There have been numerous biomarkers and risk factor scores that have been studied for their ability to predict neonatal AKI. To move towards personalized medicine, neonatal AKI must be categorized into phenotypes and subphenotypes that fully encapsulate the diverse causes and specific treatments. This review aims to advance our understanding of neonatal AKI detection through the use of biomarkers, subphenotypes, and phenotypes to move towards personalized treatment strategies.

The Complete Blood Count: A Practical Tool for the Pediatrician.

Every child should have a baseline hematology evaluation with hemoglobin and hematocrit levels starting at age 12 months, or younger if clinically indicated. Although history and physical examination provide key information needed to diagnose blood disorders, the addition of a complete blood count (CBC) with differential count and reticulocyte count allows the clinician to narrow the differential diagnosis and tailor the subsequent evaluation. The interpretation of CBC results is a skill that requires practice. Every clinician can learn to identify possible diagnoses before consulting a specialist. This review provides a step-by-step approach for CBC interpretation with tools to help the clinician diagnose and interpret the most common blood disorders seen in the general pediatric clinic or inpatient setting.

Chrysin inhibits propagation of HeLa cells by attenuating cell survival and inducing apoptotic pathways.

OBJECTIVE: Chrysin, one of the main active constituents of flavonoids, is known for demonstrating protective effects against various types of cancer including cervical cancer. The aim of this study was to determine apoptosis induction and antiproliferative action of chrysin on human cervical cancer cells. MATERIALS AND METHODS: In this study, attempts have been made to establish anticancer role of chrysin on HeLa cells. MTT, mitochondrial potential, DNA fragmentation, annexin V/propidium iodide assays, qPCR and protein profiling were performed. RESULTS: Chrysin treated HeLa cells showed time and dose dependent decrease in cell viability and demonstrated profound effects on nuclear morphology and DNA fragmentation. Chrysin treatment increased the expression of proapoptotic genes BAD, BAX, BID, BOK and APAF1, TNF, FASL, FAS, FADD and caspases (like caspase 3, caspase 7, caspase 8 and caspase 9), whereas it decreased the expression level of antiapoptotic genes MCL-1, NAIP, XIAP and Bcl-2 and cell cycle regulatory genes CCNB1, CCNB2, CCND1, CCND2, CCND3, CCNE2, CDK4 and CDK2 at transcript level. Furthermore, chrysin significantly upregulated pro-apoptotic proteins, like TRAILR2/DR5, TRAILR1/DR4, Fas/TNFRSF6/CD95, phosphoP53(S15), BAD, BAX, cleaved caspase 3, procaspase 3, HTRA2/Omi and SMAC/Diablo, while downregulated anti-apoptotic proteins like BCL-X, BCL2, XIAP and CIAPs that support chrysin mediated apoptosis in HeLa cells. Remarkably, chrysin downregulated the phosphorylated AKT pathway proteins, (p-473) AKT, (p-Ser 2448) mTOR, (p-Ser241) PDK1, (p-Ser112) BAD, and upregulated (p-Ser21) GSK3b, (p-Thr172) AMPKa, P27 (p-Thr198) and (p-Ser15) P53, which endorses chrysin mediated apoptosis. CONCLUSIONS: Chrysin significantly inhibited proliferation and induced apoptosis by modulation of various apoptotic genes and AKT/MAPK pathway genes.

Renal cystic diseases during the perinatal and neonatal period.

Renal cystic diseases are a clinically and genetically diverse group of renal diseases that can manifest in utero, infancy, or throughout childhood and adulthood. These diseases may be unilateral or bilateral with a single cyst or multiple cysts, or with increased echogenicity of the renal cortex without macroscopic cysts. Certain cystic renal diseases are life-threatening, with many developing chronic kidney and hepatic disease if not recognized early enough. Therefore, due to the prevalence and life-altering complications of this specific group of diseases in vulnerable populations, it is crucial for clinicians and healthcare providers to have an overall understanding of cystic diseases and how to pre-emptively detect and manage these conditions. In this review, we discuss in detail the epidemiology, genetics and pathophysiology, diagnosis, presentation, and management of numerous genetic and sporadic renal cystic diseases, such as polycystic kidney disease, multicystic dysplastic kidney, and calyceal diverticula, with an emphasis on prenatal care and pregnancy counseling.

Phytochemicals induce apoptosis by modulation of nitric oxide signaling pathway in cervical cancer cells.

OBJECTIVE: Nitric Oxide (NO) is produced by NO synthases (NOS) and is a key signaling molecule that regulates tumorigenesis, both aiding and alleviating it. Elevated NO levels are cytotoxic to cancer cells, making NOS an important target for cancer treatment. In the present study, the modulatory effects of the phytochemicals, quercetin, sulforaphane, genistein, and epigallocatechin-3-gallate on NO pathway and apoptosis were shown in HeLa cervical cancer cells. MATERIALS AND METHODS: Fluorescent microscopy and flow cytometry were used to assess apoptosis. A Griess assay was used to quantitatively measure NO, quantitative PCR array was used to assess the expression levels of genes involved in the NO signaling pathway, and immunocytochemistry was used to determine NOS protein expression. The functional association among the modulated genes was evaluated using network biology analysis, gene set enrichment, and KEGG pathway analysis. RESULTS: Treatment with the phytochemicals elevated NO levels in HeLa cells and modulated various genes involved in nitric oxide biosynthesis, superoxide metabolism, and oxidative stress, including NOS1, NOS2, NOS3, ALOX12, and SOD2, with a concomitant increase in NOS2 and NOS3 protein expression levels; also, the phytochemicals were found to induce apoptosis. CONCLUSIONS: These results suggest that the phytochemical-induced cell death is partially attributed to the activation of the NO pathway and upregulation of pro-oxidant ROS generators. Further experimental studies are required to explore this mechanistic association of NO signaling pathway activation and induction of apoptosis in other types of cancer.

Pericardial Effusion and Tamponade Complicating Acute Pericarditis in a Human Metapneumovirus-Infected Adult: A Unique Case Report.

Acute pericarditis (AP), or pericardial sac inflammation, is a self-limited condition in healthy individuals. Viruses, including adenoviruses, enteroviruses, cytomegalovirus, and influenza virus, have been well documented to cause AP. In contrast, human metapneumovirus (hMPV), a relatively newer virus, has been described in a few cases to cause serious cardiac complications. Here we report a patient who developed an imminent cardiac tamponade associated with hMVP respiratory infection.

Molecular and epidemiologic characterization of Wilms tumor from Baghdad, Iraq.

BACKGROUND: Wilms tumor (WT) is the most common childhood kidney cancer worldwide, yet its incidence and clinical behavior vary according to race and access to adequate healthcare resources. To guide and streamline therapy in the war-torn and resource-constrained city of Baghdad, Iraq, we conducted a first-ever molecular analysis of 20 WT specimens to characterize the biological features of this lethal disease within this challenged population. METHODS: Next-generation sequencing of ten target genes associated with WT development and treatment resistance (WT1, CTNNB1, WTX, IGF2, CITED1, SIX2, p53, N-MYC, CRABP2, and TOP2A) was completed. Immunohistochemistry was performed for 6 marker proteins of WT (WT1, CTNNB1, NCAM, CITED1, SIX2, and p53). Patient outcomes were compiled. RESULTS: Mutations were detected in previously described WT "hot spots" (e.g., WT1 and CTNNB1) as well as novel loci that may be unique to the Iraqi population. Immunohistochemistry showed expression domains most typical of blastemal-predominant WT. Remarkably, despite the challenges facing families and care providers, only one child, with combined WT1 and CTNNB1 mutations, was confirmed dead from disease. Median clinical follow-up was 40.5 months (range 6-78 months). CONCLUSIONS: These data suggest that WT biology within a population of Iraqi children manifests features both similar to and unique from disease variants in other regions of the world. These observations will help to risk stratify WT patients living in this difficult environment to more or less intensive therapies and to focus treatment on cell-specific targets.

Targeting renin-angiotensin system in malignant hypertension in atypical hemolytic uremic syndrome.

Hypertension is common in hemolytic uremic syndrome (HUS) and often difficult to control. Local renin-angiotensin activation is believed to be an important part of thrombotic microangiopathy, leading to a vicious cycle of progressive renal injury and intractable hypertension. This has been demonstrated in vitro via enhanced tissue factor expression on glomerular endothelial cells which is enhanced by angiotensin II. We report two pediatric cases of atypical HUS with severe refractory malignant hypertension, in which we targeted the renin-angiotensin system by using intravenous (IV) enalaprilat, oral aliskiren, and oral enalapril with quick and dramatic response of blood pressure. Both drugs, aliskiren and IV enalaprilat, were effective in controlling hypertension refractory to multiple antihypertensive medications. These appear to be promising alternatives in the treatment of severe atypical HUS-induced hypertension and hypertensive emergency.

Eculizumab for atypical hemolytic-uremic syndrome in India: First report from India and the challenges faced.

Much progress has been made in understanding the pathophysiology and treatment of atypical hemolytic uremic syndrome (aHUS). Plasma therapy is the mainstay of treatment for aHUS. The availability of the first effective anti-complement therapeutic agent, eculizumab, has dramatically changed the outlook of this disease. However, its use in clinical practice raises important questions, such as who should receive the drug, when to start such therapy, and is it safe to stop treatment once the disease is controlled. We describe here for the 1st time in India, use of eculizumab in a 12-year-old boy with aHUS. We also describe in this report challenges faced in procuring the drug, and an ideal, evidence-based method of treating aHUS in children.

Desmoplastic Small Round Cell Tumor of the Kidney: AIRP Best Cases in Radiologic-Pathologic Correlation.

Editor's Note.-RadioGraphics continues to publish radiologic-pathologic case material selected from the American Institute for Radiologic Pathology (AIRP) "best case" presentations. The AIRP conducts a 4-week Radiologic Pathology Correlation Course, which is offered five times per year. On the penultimate day of the course, the best case presentation is held at the American Film Institute Silver Theater and Cultural Center in Silver Spring, Md. The AIRP faculty identifies the best cases, from each organ system, brought by the resident attendees. One or more of the best cases from each of the five courses are then solicited for publication in RadioGraphics. These cases emphasize the importance of radiologic-pathologic correlation in the imaging evaluation and diagnosis of diseases encountered at the institute and its predecessor, the Armed Forces Institute of Pathology (AFIP).

Tenosynovial chondromatosis of the flexor hallucis longus in a 17-year-old girl.

Tenosynovial chondromatosis is a benign chondrogenic metaplasia of extra-articular synovial tissue. The most common locations for tenosynovial chondromatosis to develop are the hands and feet. The condition has rarely been reported in children. We present a case of tenosynovial chondromatosis of the flexor hallucis longus in a 17-year-old girl. The presentation was unusual not only due to the location and young age of the patient but also the absence of any palpable mass on physical exam and complete lack of calcification of the cartilage bodies. Initial diagnosis was made by MRI. The patient underwent tenosynovectomy with an excellent postoperative recovery at 6-month follow-up. Histopathology confirmed the diagnosis of tenosynovial chondromatosis.

Haematolohical profile of subacute oral toxicity of molybdenum and ameliorative efficacy of copper salt in goats.

Molybdenum toxicity produces a state of secondary hypocuprosis, resulting into alterations in normal hematological profile. In the present study, ammonium molybdate alone and with copper sulfate (II) pentahydrate (ameliorative agent) was administered orally for 30 consecutive days in healthy goats of group 1 and 2, respectively, to access the effect on the hematological profile on different predetermined days of dosing. Administration of ammonium molybdate alone produced significant decline in the mean values of hemoglobin (Hb), packed cell volume (PCV), total leukocyte count (TLC), total erythrocyte count (TEC), and mean corpuscular hemoglobin concentration (MCHC), with a significant increase in neutrophil level and mean corpuscular volume (MCV). However, values of erythrocyte sedimentation rate, mean corpuscular hemoglobin, and differential leukocyte count were not significantly altered. On comparing observations of ameliorative group with the group 1 goats, it is concluded that the ameliorative copper salt has beneficial effects in alleviating the alterations in the values of Hb, PCV, TLC, TEC, MCV, MCHC, and neutrophils.

Disposition kinetics and urinary excretion of ciprofloxacin in goats following single intravenous administration.

We evaluated the pharmacokinetics of ciprofloxacin in serum (n = 6) and urine (n = 4) in goats following a single intravenous administration of 4 mg/kg body weight. The serum concentration-time curves of ciprofloxacin were best fitted by a two-compartment open model. The drug was detected in goat serum up to 12 h. The elimination rate constant (beta) and elimination half-life (t1/2beta) were 0.446 +/- 0.04 h(-1) and 1.630 +/- 0.17 h, espectively. The apparent volume of distribution at steady state (Vdss) was 2.012 +/- 0.37 l/kg and the total body clearance (ClB) was 16.27 +/- 1.87 ml/min/kg. Urinary recovery of ciprofloxacin was 29.70% +/- 10.34% of the administered dose within 36 h post administration. In vitro serum protein binding was 41% +/- 13.10%. Thus, a single daily intravenous dose of 4 mg/kg is sufficient to maintain effective levels in serum and for 36 h in urine, allowing treatment of systemic, Gram-negative bacterial infections and urinary tract infections by most pathogens.

Early penile rehabilitation following radical prostatectomy: Cleveland clinic experience.

Erectile dysfunction is one of the most important quality of life issues following radical prostatectomy. The potency rates reported following nerve-sparing technique varies between 40 and 86%, and the time period required for complete recovery of erectile function varies from 6 to 24 months. The literature evidence suggests that lack of natural erections during this period of time produces cavernosal hypoxia. Prolonged periods of cavernosal hypoxia induce fibrosis, which later increases the incidence of venous leak. Recently, there is a growing interest among the physicians to interrupt these events by preventing cavernosal hypoxia during the period of neuropraxia. Initial studies using intracavernosal injection appears to be beneficial. In this article, we reviewed the pathophysiology of cavernosal hypoxia following radical prostatectomy with currently available evidence for the interventions to promote the nerve recovery and regeneration.

Electroantennogram responses of the potato tuber moth, Phthorimaea operculella (Lepidoptera; Gelichiidae)to plant volatiles.

Electroantennograms (EAGs)were recorded from males and females of the potato tuber moth,Phthorimaea operculella in response to a broad range of plant volatile compounds belonging to diverse chemical classes.The responses to 27 compounds were evaluated,which indicated significant differences in EAGs between chemicals as well as between sexes.The fatty acid derivatives comprising essentially green leaf volatile components elicited significantly greater responses in females.The response profile of males was,in general,lower than that of females.EAG responses to the oxygenated and hydrocarbon monoterpenes were lower in both males and females.Dose -response studies indicate differences in response between the sexes and concentrations,suggesting the existence of sexual dimorphism. Compounds belonging to the fatty acid derivatives class appear to be important for an oligophagous pest such as the potato tuber moth and the findings are discussed in relation to host plant selection in this species.

Early combination therapy: intracavernosal injections and sildenafil following radical prostatectomy increases sexual activity and the return of natural erections.

Early pharmacological prophylaxis has been reported to increase the return of spontaneous erections following radical prostatectomy (RP). In this study, we evaluated the role of intracavernosal alprostadil (PGE1) combined with sildenafil in stimulating early recovery of spontaneous erections following RP. In this prospective study, we included 22 patients who underwent bilateral nerve-sparing RP after October 2004. Sildenafil dose of 50 mg/day was started at the time of hospital discharge. Of 22 patients, 18 started on PGE1-4 microg (1-8) and four started on low-dose Trimix (20 U) 2-3 times/week. These patients are followed up at regular intervals (3, 6, 9 and 12 months) with abridged version of the International Index for Erectile Function-5 questionnaire. Patient compliance, return of sexual activity and return of natural erection, adverse effects and reasons for discontinuation were recorded. Penile doppler studies were performed during followup visits to assess the vascular status. After a mean followup of 6 months (3-8 months), 11/22 (50%) patients had return of spontaneous partial erections. Of the 18 PGE1 users, six continued 4 microg PGE1, four increased the dose to 8 microg, six decreased the dose to 2 microg and two patients further reduced the dose to 1 microg. Of four low-dose Trimix users, three increased the dose to 30 U and one reduced the dose to 15 U. Of 22 patients, 21 were sexually active: 12/21 (57%) with the injections alone and 9/21 (42.9%) with combination therapy (injections (PGE1) and sildenafil). Penile doppler studies revealed arterial insufficiency in 77% (17/22) patients and venous insufficiency in one patient. Early intracavernosal injections following RP facilitated early sexual intercourse, patient satisfaction and potentially earlier return of natural erections. Early combination therapy with sildenafil allowed a lower dose of intracavernous injections, minimizing the penile discomfort.

Sexual dysfunction after pelvic surgery.

Pelvic surgeries are among the most common causes of organic sexual dysfunction in men and women. The impact of nerve-sparing surgery on potency has been well documented in radical prostatectomy. However, its impact on potency needs to be evaluated in other pelvic surgeries. Sexual dysfunction is highly prevalent even after multiple technical advances in the field of oncological surgeries. The prevalence varies from 8 to 82%, depending on the type of pelvic surgery. In females, sexual dysfunction has not been evaluated adequately using validated questionnaires. However, in subspecialized circles, treatment for female sexual dysfunction is becoming routine. Currently, physicians have several options for the treatment of erectile dysfunction (ED) in men. Since the introduction of oral PDE-5 inhibitors, oral therapy has become the first-line treatment option for ED, irrespective of etiology. Currently available treatment options for the female sexual dysfunction include estrogens, androgens, phosphodiesterase inhibitors, and dopamine receptor antagonists. Initial reports regarding the role of early rehabilitation are encouraging and may become the part of routine practice in the management of ED after pelvic surgery. In this article, we summarize the sexual dysfunction following pelvic surgeries and their management.

Early use of vacuum constriction device following radical prostatectomy facilitates early sexual activity and potentially earlier return of erectile function.

To assess the efficacy of vacuum constriction devices (VCD) following radical prostatectomy (RP) and determine whether early use of VCD facilitates early sexual activity and potentially earlier return of erectile function. This prospective study consisted of 109 patients who underwent nerve-sparing (NS) or non-nerve-sparing (NNS) RP between August 1999 and October 2001 and developed erectile dysfunction following surgery. The patients were randomized to VCD use daily for 9 months (Group 1, N=74) or observation without any erectogenic treatment (Group 2, N=35). Treatment efficacy was analyzed by responses to the Sexual Health Inventory of Men (SHIM) (abridged 5-item International Index of Erectile Function (IIEF-5)), which were stratified by the NS status. Patient outcome regarding compliance, change in penile length, return of natural erection, and ability for vaginal intercourse were also assessed. The mean patient age was 58.2 years, and the minimum follow-up was 9 months. Use of VCD began at an average of 3.9 weeks after RP. In Group 1, 80% (60/74) successfully used their VCD with a constriction ring for vaginal intercourse at a frequency of twice/week with an overall spousal satisfaction rate of 55% (33/60). In all, 19 of these 60 patients (32%) reported return of natural erections at 9 months, with 10/60 (17%) having erections sufficient for vaginal intercourse. The abridged IIEF-5 score significantly increased after VCD use in both the NS and NNS groups. After a mean use of 3 months, 14/74 (18%) discontinued treatment. In Group 2, 37% (13/35) of patients regained spontaneous erections at a minimum follow-up of 9 months after surgery. However, only four of these patients (29%) had erections sufficient for successful vaginal intercourse and rest of patients (71%) sought adjuvant treatment. Of the 60 successful users, 14 (23%) reported a decrease in penile length and circumference at 9 months (range, 4-8 months) compared to 12/14 (85%) among the nonresponders. However, in control group 22/35 reported decrease in penile length and circumference. Early use of VCD following RP facilitates early sexual intercourse, early patient/spousal sexual satisfaction, and potentially an earlier return of natural erections sufficient for vaginal penetration.

Role of nitric oxide in ovarian follicular development and egg production in Japanese quail (Coturnix coturnix japonica).

Role of nitric oxide (NO) in regulating the reproductive functions at hypothalamo-hypophysealovarian axis in Japanese quail was studied. In first experiment, metabolites of NO, i.e. nitrite and nitrate (NO2 and NO3) were estimated together in hypothalamus, serum and ovarian follicles of good and poor layers. In the second experiment, different NO modulators such as L-arginine (L-Arg), sodium nitroprusside (SNP) and N(G)-nitro-L-arginine methyl ester, HCl (L-NAME) were administered to the birds. In the first experiment, significantly higher (P < 0.01) NO2 and NO3 levels in serum, hypothalamus and largest (F1) ovarian follicles were observed in good layers as compared to poor layers. Higher (P < 0.05) NO2 and NO3 concentration was observed in F1 follicles than smaller follicles (F2) only in good layers. The NO2 and NO3 concentration was significantly reduced (P < 0.05) in post ovulatory follicles (POFs) in comparison to F1 and F2 follicles. In the second experiment, the serum NO2 and NO3 concentrations were higher (P < 0.05) in the SNP, lower (P < 0.05) in the L-Name group and unchanged in the L-Arg treated group in comparison to control group. compared to control, L-Arg and SNP increased (P < 0.05) the hypothalamic NO2 and NO3 concentration where as L-NAME reduced (P < 0.05) these levels. The NO2 and NO3 concentration was increased (P < 0.05) as the follicle size increased and it was significantly reduced (P < 0.05) in POFs. The higher (P < 0.05) follicular NO2 and NO3 concentration was observed in L-Arg group in comparison to control group. Egg production was also found to be higher (P < 0.05) in L-Arg group whereas it was not different (P > 0.05) in SNP and L-NAME treated groups. The yolk weight and yolk to albumin ratio was reduced (P < 0.05) in L-NAME group in comparison to control group. It may be concluded from the present study that NO plays a key role in regulating follicular development, ovulatory mechanisms and egg production in Japanese quail.