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Nazri Mohd Yusof,1 Ayman K Saleh,2,3 Ibrahim Elsayed Abdellatif A Abuomira,4 Abdehamid A Attallah,2 Ehab Abdelftah Elshal,4 Amr abdelhalem Amr khames4 1Advanced Trauma and Limb Reconstructive Surgery Department, International Islamic University of Malaysia, Gombak, Malaysia; 2Department of Orthopedic Surgery, Faculty of Medicine for Girls, Al-Azhar University, Cairo, Egypt; 3Department of Surgery, College of Medicine, Prince Sattam bin Abdulaziz University, Al-Kharj, Saudi Arabia; 4Department of Orthopaedic surgery, Al-Azhar University, Assiut, EgyptCorrespondence: Ayman K Saleh, Email aymankamal37@gmail.comBackground and Aim: Maintenance of stability using external fixation devices is an important principle to ensure successful treatment of osteomyelitis (OM). In this study, we report our experience with femoral OM treated with acute compression and bone transport using the Orthofix limb reconstruction system (LRS).&#x00A0Patients and Methods: This prospective study included 30 consecutive patients with femoral OM. LRS insertion and corticotomy were done according to the standard technique. Radiographic evaluation was performed every 2 weeks during the distraction phase and every 2– 4 weeks during the consolidation phase. The clinical outcome measurements included union time, limb length discrepancy, additional operative procedures, refracture and infection.Results: The present study included 30 patients with femoral OM. They comprised 27 males (90.0%) and 3 females (10.0%) with an age of 28.1 ± 15.6 years. All, except one, achieved union with a mean union time of 8.6 months (range 4– 20 months). The mean union time for acute compression was 7.6 months (range 4– 20 months) while for patients with bone transport it was 14.5 months (range 12– 18 months). The mean limb length discrepancy was 1.8 cm (range 0– 4 cm). At the end of the follow=up, two patients were not able to ambulate without support; one due to non-union and one due to paraplegia.Conclusion: The present study identified treatment of femoral OM using LRS as a feasible and effective technique with good outcomes. Reported complications could be adequately managed in most cases.Keywords: osteomyelitis, external fixation, limb reconstruction system

Purpose: Treatment of osteomyelitis (OM) is challenging. Ilizarov bone transport is a commonly used technique for management of OM. The recently introduced limb reconstruction system (LRS) has been effectively used for management of OM. It was suggested to be easier in use and less invasive. The present retrospective study aimed to compare LRS and Ilizarov bone transport in management of femoral OM using a propensity score matched analysis., Methods: The present retrospective study included 80 consecutive patients with femoral OM. The studied patients were managed either using Ilizarov external fixator ( n  = 40) or Orthofix LRS ( n  = 40). The clinical outcome measurements included union time, limb length discrepancy, additional operative procedures, refracture and infection., Results: Patients in the LRS group were exposed to significantly higher frequency of bone transport (30.0 versus 15.0%) and lower frequency of acute compression and lengthening (10.0 versus 32.5%). Patients in Ilizarov group had significantly higher frequency of tobramycin pellets as compared to their counterparts. The studied groups were comparable regarding the operative complications including pin-tract infection, non-union at docking site and refracture. Patients in the Ilizarov had significantly shorter time to union (8.2 ± 3.2 versus 11.0 ± 5.6 months, p  = 0.012). No statistically significant differences were found between the studied groups regarding the quality-of-life domains., Conclusions: Use of Ilizarov external fixator and Orthofix LRS devices proved to be effective and reliable. Their influences on patients' quality appear to be comparable., Competing Interests: Conflict of InterestThe authors declare that they have no conflict of interest., (© Indian Orthopaedics Association 2024. Springer Nature or its licensor (e.g. a society or other partner) holds exclusive rights to this article under a publishing agreement with the author(s) or other rightsholder(s); author self-archiving of the accepted manuscript version of this article is solely governed by the terms of such publishing agreement and applicable law.)

Introduction: Frozen shoulder is a very common musculoskeletal condition and the evidence related to the additional effects of extracorporeal shockwave therapy (ESWT) with intra-articular (IA) lidocaine injection in individuals with frozen shoulder is rare. Therefore, this study aims to compare and investigate the additional effects of extracorporeal shockwave therapy (ESWT) with intra-articular (IA) lidocaine injection in a frozen shoulder., Methods: Sixty eligible participants with frozen shoulder were included and the active group (n = 30, age 52.12 ± 5.2 years) received a lidocaine injection (1% lidocaine (Xylocaine) and 2cc (80 mg) methylprednisolone acetate) with active ESWT (3.5 bar air pressure and 2000 pulses with an energy flux density (EFD) ¼ 0.16 mJ/mm 2 ) three sessions a week for 4 weeks. The placebo group (n = 30, age 53.56 ± 5.5 years) received lidocaine injection with placebo treatment (a special head that blocked the shock waves) three sessions a week for 4 weeks. Both groups received progressive resistance exercises (PRE) to the shoulder muscles. The primary outcome was pain intensity, measured with the visual analogue scale. The other outcome measures were the thickness of the coracohumeral ligament (CHL) measured by magnetic resonance imaging (MRI), abduction, and lateral rotation range of motion (ROM), functional disability, kinesiophobia, depression status, and quality of life. Participants were assessed at baseline, after 4 weeks, 8 weeks, and at 6-month follow-up., Results: The post-intervention at 4 weeks showed an improvement of 2.0 (CI 95% 1.71-2.28) in the active group compared to the placebo group. Similar effects were noted after 8 weeks (2.2) (CI 95% 1.91-2.48) and at the 6-month (1.9) (CI 95% 1.61-2.18) follow-up. Similar improvements were also found in the thickness of the CHL ligament (0.6) (CI 95% 0.46-0.73), abduction and lateral rotation (ROM) (- 23.6) (CI 95% - 27.47 to -19.72), (- 18.10) (CI 95% - 19.72 to - 16.47), functional disability (16.2) (CI 95% 14.85-17.54), kinesiophobia (11.0 (CI 95% 10.21-11.98), depression status (4.4) (CI 95% 4.03-4.76) and quality of life (0.9) (CI 95% 0.79-1.00) (p = 0.001) at the 6-month follow-up period, where mean estimates and their confidence intervals all included worthwhile effects. There were no adverse reactions or side effects noted in either the active or placebo groups during and after the treatment., Conclusions: The study concluded that the addition of extracorporeal shockwave therapy after intra-articular lidocaine injection improves pain, functional disability, range of motion, kinesiophobia, depression status, and quality of life in people with frozen shoulder., Trial Registration: https://ctri.nic.in , identifier; CTRI/2020/04/024834 prospectively registered on 24/04/2020., (© 2024. The Author(s).)

Background: There is ample evidence supporting the use of different manipulative therapy techniques for Cervicogenic Headache (CgH). However, no technique can be singled as the best available treatment for patients with CgH. Therefore, the objective of the study is to find and compare the clinical effects of cervical spine over thoracic spine manipulation and conventional physiotherapy in patients with CgH., Design, Setting, and Participants: It is a prospective, randomized controlled study conducted between July 2020 and January 2023 at the University hospital. N = 96 eligible patients with CgH were selected based on selection criteria and they were divided into cervical spine manipulation (CSM; n = 32), thoracic spine manipulation (TSM; n = 32) and conventional physiotherapy (CPT; n = 32) groups, and received the respective treatment for four weeks. Primary (CgH frequency) and secondary CgH pain intensity, CgH disability, neck pain frequency, neck pain intensity, neck pain threshold, cervical flexion rotation test (CFRT), neck disability index (NDI) and quality of life (QoL) scores were measured. The effects of treatment at various intervals were analyzed using a 3 × 4 linear mixed model analysis (LMM), with treatment group (cervical spine manipulation, thoracic spine manipulation, and conventional physiotherapy) and time intervals (baseline, 4 weeks, 8 weeks, and 6 months), and the statistical significance level was set at P < 0.05., Results: The reports of the CSM, TSM and CPT groups were compared between the groups. Four weeks following treatment CSM group showed more significant changes in primary (CgH frequency) and secondary (CgH pain intensity, CgH disability, neck pain frequency, pain intensity, pain threshold, CFRT, NDI and QoL) than the TSM and CPT groups (p = 0.001). The same gradual improvement was seen in the CSM group when compared to TSM and CPT groups (p = 0.001) in the above variables at 8 weeks and 6 months follow-up., Conclusion: The reports of the current randomized clinical study found that CSM resulted in significantly better improvements in pain parameters (intensity, frequency and threshold) functional disability and quality of life in patients with CgH than thoracic spine manipulation and conventional physiotherapy., Trial Registration: Clinical trial registration: CTRI/2020/06/026092 trial was registered prospectively on 24/06/2020., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2024 Nambi et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

The high rate of microbes and their biological activity in the patient's mouth is a concern in the domains of dental caries and periodontal disease. The study aimed to shed light on the relationship between graphene oxide's nanoparticles (nGOs) antimicrobial properties and the growth of dental pathogenic bacteria. The forty swab samples were frequently collected from the patient's cavity mouth between November 2019 and January 2020, from patients who visited dentist clinics in Baghdad by taking swabs from mouth cavities with various dental caries with two age groups (5-17) and (18-60) from male and female to streaking them on Brain-Heart Infusion (BHI) agar, then identified by re-streaking on Mitis Salivarius Bacitracin (MSB) agar. All isolates were confirmed as Streptococcus mutans after API 20 Strep method. As well as the Colony Forming Units (CFU) were then determined after diluting the bacterial cell suspensions to obtain cell samples containing 1.5 × 108 CFU/ ml. The collagen-binding adhesin (cnm) and glucosyltransferases (gtf) of S. mutans genes were identified using polymerase chain reaction (PCR) method before and after exposure to the nGOs, which were prepared in different pulse laser energy (500, 600, and 700 mJ) with presence and absence of the magnetic field, and the data have been analyzing. After counting the CFU, the nGOs shows high effectiveness inhibiting the growth of S. mutans. This research provides definitive answers about the relationship between nGOs, antibacterial caries, and periodontal disease., (© 2023. The Author(s), under exclusive licence to The Society of The Nippon Dental University.)

Chronic non-specific low back pain (CNLBP) is the most common musculoskeletal problem. The purpose of this study was to investigate the effects of advanced physiotherapeutic exercise programs on imaging findings and inflammatory biomarkers in soccer players with CNLBP. In total, 60 CNLBP participants were divided into virtual reality exercise (VRE; n = 20), isokinetic exercise (IKE; n = 20), and conventional exercise ( n = 20) groups. Pain intensity, imaging findings (muscle cross-sectional area (CSA) and muscle thickness), and changes in inflammatory biomarkers (CRP, TNF-α, IL-2, IL-4, and IL-6) were measured at baseline and after four weeks. After four weeks of intervention, there was a significant improvement ( p = 0.001) in pain intensity for the VRE vs. IKE (0.7; CI 95% 0.38 to 1.07) and VRE vs. conventional (3.0 CI 95% 2.68 to 3.31) groups. The IKE group showed a greater number of significant changes in muscle CSA and muscle thickness than the other two groups ( p < 0.001). Moreover, the VRE group showed significant improvement in inflammatory biomarker measures compared with the other two groups ( p < 0.001). In CNLBP, virtual and isokinetic exercises had equal effects on reducing pain intensity. Isokinetic exercise is beneficial in increasing the muscle CSA and thickness, and virtual exercises are helpful for attenuating the inflammation process in soccer players with CNLBP.

Loss of fatty acid β-oxidation (FAO) in the proximal tubule is a critical mediator of acute kidney injury and eventual fibrosis. However, transcriptional mediators of FAO in proximal tubule injury remain understudied. Krüppel-like factor 15 (KLF15), a highly enriched zinc-finger transcription factor in the proximal tubule, was significantly reduced in proximal tubule cells after aristolochic acid I (AAI) treatment, a proximal tubule-specific injury model. Proximal tubule specific knockout of Klf15 exacerbated proximal tubule injury and kidney function decline compared to control mice during the active phase of AAI treatment, and after ischemia-reperfusion injury. Furthermore, along with worsening proximal tubule injury and kidney function decline, knockout mice exhibited increased kidney fibrosis as compared to control mice during the remodeling phase after AAI treatment. RNA-sequencing of kidney cortex demonstrated increased transcripts involved in immune system and integrin signaling pathways and decreased transcripts encompassing metabolic pathways, specifically FAO, and PPARα signaling, in knockout versus control mice after AAI treatment. In silico and experimental chromatin immunoprecipitation studies collectively demonstrated that KLF15 occupied the promoter region of key FAO genes, CPT1A and ACAA2, in close proximity to transcription factor PPARα binding sites. While the loss of Klf15 reduced the expression of Cpt1a and Acaa2 and led to compromised FAO, induction of KLF15 partially rescued loss of FAO in AAI-treated cells. Klf15, Ppara, Cpt1a, and Acaa2 expression was also decreased in other mouse kidney injury models. Tubulointerstitial KLF15 independently correlated with eGFR, PPARA and CPT1A appearance in expression arrays from human kidney biopsies. Thus, proximal tubule-specific loss of Klf15 exacerbates acute kidney injury and fibrosis, likely due to loss of interaction with PPARα leading to loss of FAO gene transcription., (Copyright © 2021 International Society of Nephrology. Published by Elsevier Inc. All rights reserved.)

Altered cellular metabolism in kidney proximal tubule (PT) cells plays a critical role in acute kidney injury (AKI). The transcription factor Krüppel-like factor 6 (KLF6) is rapidly and robustly induced early in the PT after AKI. We found that PT-specific Klf6 knockdown ( Klf6 PTKD ) is protective against AKI and kidney fibrosis in mice. Combined RNA and chromatin immunoprecipitation sequencing analysis demonstrated that expression of genes encoding branched-chain amino acid (BCAA) catabolic enzymes was preserved in Klf6 PTKD mice, with KLF6 occupying the promoter region of these genes. Conversely, inducible KLF6 overexpression suppressed expression of BCAA genes and exacerbated kidney injury and fibrosis in mice. In vitro , injured cells overexpressing KLF6 had similar decreases in BCAA catabolic gene expression and were less able to utilize BCAA. Furthermore, knockdown of BCKDHB , which encodes one subunit of the rate-limiting enzyme in BCAA catabolism, resulted in reduced ATP production, while treatment with BCAA catabolism enhancer BT2 increased metabolism. Analysis of kidney function, KLF6 , and BCAA gene expression in human chronic kidney disease patients showed significant inverse correlations between KLF6 and both kidney function and BCAA expression. Thus, targeting KLF6-mediated suppression of BCAA catabolism may serve as a key therapeutic target in AKI and kidney fibrosis., Competing Interests: Competing interest statement: J.C.H. declares a Shangpharma research grant of $250,000 per year in 2019 to 2020 and is a Scientific Advisory Board member for RenalytixAI.

Background: Small-sized HCC can be effectively cured by surgery with good clinical outcomes. A highly sensitive HCC α-fetoprotein routine test (HCC-ART) for HCC diagnosis as well as a simplied form of the HCC-ART were reported in the British Journal of Cancer. Here, we verified and studied the applicability of the HCC-ART to the detection of early-stage HCC., Methods: 341 cirrhotic patients and 318 HCC patients were included in this study. For each, the HCC-ART score was calculated, and then the sensitivity, specificity, and results of an ROC curve analysis were compared between the HCC-ART and AFP when these biomarkers were used to detect small-sized HCC., Results: Different HCC-ART cutoffs were set for the detection of different tumor sizes. The HCC-ART (AUC = 0.871, 70% sensitivity, 97% specificity) and the simplified HCC-ART (AUC = 0.934, 82% sensitivity, 100% specificity) were found to have high predictive power when attempting to separate cirrhotic patients from those with small-sized HCC. The simplified HCC-ART score was superior to AFP for determining stages according to the early Okuda (0.950 AUC, 84% sensitivity, 99% specificity), CLIP (0.945 AUC, 84% sensitivity, 99% specificity), and BCLC (1.000 AUC, 100% sensitivity, 99% specificity) staging systems. The simplified HCC-ART score was more strongly correlated than AFP and other staging systems with HCC tumor size (P < 0.0001; r = 0.8)., Conclusion: The HCC-ART is superior to AFP for diagnosing early-stage HCC. Due to its advantages of minimal variability and a wide continuous scale for assessing HCC severity, the simplified HCC-ART has the potential to be more widely used than the original HCC-ART.

Background: There is controversial data in the literature about the characteristics and features of dual hepatitis B and hepatitis C infection. This work is concerned with estimating the extent to which HBV could influence circulating levels of hepatitis C viral nonstructural-4 (HCV-NS4) in addition to some direct fibrosis markers in chronic hepatitis C., Methods: Thirty-eight HCV mono-infected and 87 HCV/HBV co-infected patients constituted this study. Western-blot and ELISA were used for identifying HCV-NS4, hepatitis B surface antigen (HBsAg), collagen III and matrixmetalloproteinase-1 (MMP-1) in patients' sera., Results: Hepatitis B surface antigen (HBsAg) provided area under curve (AUC) of 0.97 for identifying HBV-patients with 89% sensitivity and 94% specificity, while HCV-NS4 antigen provided an AUC of 0.95 for identifying HCV-patients with 89% sensitivity and absolute specificity (100%). In general, patients with significant fibrosis (F2-F4) showed significantly higher concentration of collagen III (P = 0.009) and lower concentrations of MMP-1 (P = 0.007) when compared to patients with minimal fibrosis (F1). However, HCV/HBV co-infected patients with F1 and F2-F4 did not show any significant difference (P > 0.05) from HCV mono-infected patients with respect to HCV-NS4, collagen III and MMP-1. These results indicate that HBV does not influence the rate of HCV-NS4 synthesis and the deposition of extracellular matrix in HCV/HBV co-infected patients and subsequently does not affect the progression rates of hepatic fibrosis., Conclusion: HCV/HBV co-infected and HCV- mono-infected patients had similar clinical characteristics and there is no effect of HBV co-infection on the progression rates of liver fibrosis in chronic hepatitis C patients.

Hepatitis C virus (HCV)/Schistosoma mansoni coinfection is common in Egypt and other developing countries. This study aimed to investigate the influence of HCV/S. mansoni coinfection on the concentration of HCV-nonstructural protein-4 (NS4) in addition to collagen III and matrix metalloproteinase-1 (MMP-1) in different hepatic fibrosis stages. We found that coinfected patients (N = 186) showed significantly (P < 0.05, Mann-Whitney U test) higher concentrations of HCV-NS4, collagen III, and collagen III/MMP-1 ratio (CMR) than those with HCV monoinfection (N = 104) in different fibrosis stages. Conversely, coinfected patients showed significantly lower concentrations of MMP-1 when compared with HCV monoinfection. The elevated levels of CMR in case of HCV monoinfection yielded an estimated odds ratio of 1.8 and 2.6 for developing significant fibrosis (F2-F4) and cirrhosis (F4), respectively. HCV/S. mansoni coinfection increased the risk for developing F2-F4 and F4 several fold yielding an estimated odds ratio of 11.1 and 5.2, respectively. This means that coinfected patients have a 6-fold and 2-fold increased risk of developing F2-F4 and F4, respectively, over HCV-monoinfected patients. Thus, elevated levels of HCV-NS4 and CMR in HCV/S. mansoni coinfection suggest increased susceptibility of coinfected patients, compared with those with HCV monoinfection, for accelerating hepatic fibrosis progression., (© The American Society of Tropical Medicine and Hygiene.)

Conflicting results for circulating glypican-3 (GPC3) were reported in hepatocellular carcinoma (HCC) diagnosis. We aimed to improve the diagnostic power of GPC3 by developing a GPC-HCC model for diagnosing HCC. GPC3 was tested for HCC (138), liver cirrhosis (56), and fibrosis (62) patients by ELISA. Data from patient groups were retrospectively analyzed. A novel score, GPC-HCC, based on combination of GPC3 and routine laboratory tests, was developed for HCC diagnosis. The GPC-HCC model values produced a significant 1.7-fold increase in liver cirrhosis and 3.2-fold increase in HCC, in comparison with liver fibrosis. In contrast to GPC3 and alpha fetoprotein (AFP), the GPC-HCC model showed high HCC diagnostic power with area under the curve (AUC) of 0.939, sensitivity 93 %, specificity 93 %, positive predictive value 89 %, negative predictive value 95 %, and efficiency 93 %. GPC-HCC AUC in HCC with single tumor, absent vascular invasion, and tumor size ≤3 cm were 0.93, 0.92, and 0.92, respectively, compared with 0.63, 0.63, and 0.64, respectively, for GPC3 and 0.69, 0.70, 0.55, respectively, for AFP. In conclusion, owing to these promising findings, the combination of GPC3 with other laboratory simple routine tests (GPC-HCC model) could improve the diagnostic power of GPC3 in HCC screening and follow up of cirrhotic patients.

The goal of this study was to determine the levels of S. mansoni antigen in different liver fibrosis stages with chronic hepatitis C (CHC) Egyptian patients. A total of 174 CHC patients showing HCV-NS4 antigen and HCV- RNA in their sera were included. S. mansoni antigen was detected in serum using Western blot and ELISA. The levels of interferon-γ (IFN- γ) were determined using ELISA. The 50 kDa S. mansoni antigen discriminated patients infected with S. mansoni from healthy individuals with 0.93 area under curve (AUC), 92% sensitivity, and 97% specificity. The level of S. mansoni antigen (μg/ml) was significantly (P < 0.0001) increased with the progression of liver fibrosis stages (26.9 ± 17.5 in F1, 42.1 ± 25.2 in F2, 49.8 ± 30.3 in F3 and 62.2 ± 26.3 μg/mL in F4 liver cirrhosis), 26.9 ± 17.59 in significant fibrosis (F2-F4); 51.2 ± 27.9 in advanced fibrosis (F3-F4). A significant correlation (r = 0.506; P < 0.0001) was shown between the levels of the S. mansoni antigen and the HCV-NS4 antigen. In conclusion, the presence of S. mansoni antigen in different liver fibrosis stages of CHC patients confirming that concomitant schistosome infection aggravates liver disease.

The relation between interferon-gamma (IFN-γ) levels and the severity of liver diseases through fibrosis, cirrhosis, and hepatocellular carcinoma (HCC) has not been fully clarified. Thus, we aimed to characterize IFN-γ levels in liver-diseased patients. IFN-γ levels were determined by Western-blot and ELISA in sera from 30 healthy individuals, 53 patients with non-significant fibrosis (F0-F1), 47 with moderate/severe fibrosis (F2-F3), 44 cirrhotic patients (F4), and 50 with HCC. Enhanced levels of IFN-γ were associated with the progression of liver disease. The differences were statistically significant (P < 0.0001) when patients with F2-F3, F4, or HCC were compared with F0-F1 or healthy controls. The increase in IFN-γ was associated with HCC (OR = 0.98, 95% CI 0.97-0.99, P = 0.002). There was no statistically significant association between IFN-γ levels and HCV-RNA (IU/ml) (r = 0.1, P = 0.43) or HCV-NS4 (µg/mL) (r = 0.1, P = 0.17). There was significant (P < 0.0001) association between IFN-γ levels and the fibrosis stages and activity, albumin, platelet count, total bilirubin, and international normalized ratio (INR). In conclusion, elevated concentrations of IFN-γ represent a characteristic feature of liver disease severity regardless of underlying disease. Significant correlations with indices of hepatic dysfunction suggest that enhanced IFN-γ levels represent a consequence of liver dysfunction rather than of inflammatory disease.

Background: The advent of noninvasive urine-based markers as well as other novel modalities has yielded improved diagnostic accuracy. However, the new markers failed to reach higher sensitivity and specificity. We therefore evaluated the potential role of epithelial membrane antigen (EMA) and nuclear matrix protein 52 (NMP-52) singly and combined as noninvasive biomarkers for the detection of bladder cancer (BC)., Methods: A total of 160 individuals including 66 patients with BC, 54 patients with benign urologic disorders and 40 healthy volunteers were investigated. Urinary EMA at 130 kDa and NMP at 52 kDa were identified, purified and quantified by Western blot, electroelution and enzyme-linked immunosorbent assay (ELISA). The diagnostic performance of each biomarker and their combination were compared using area under receiver operating characteristic curves (AUC)., Results: Mean urinary EMA, 2.42 µg/mL, and NMP-52, 17.85 µg/mL, were significantly elevated in patients with BC compared to controls, 1.18 and 3.44 µg/mL, respectively (p&lt;0.0001). The combined use of these markers yielded values which were increased 4.4- and 13.7-fold in the benign and malignant disease groups, respectively, with respect to the normal group. The values of EMA and NMP-52 were significantly higher in patients with higher-grade tumors than those with lower-grade tumors (p&lt;0.0001). Moreover, this combination could predict all BC stages and grades with 0.91 AUC, 94% sensitivity and 80% specificity., Conclusions: EMA and NMP-52 in combination could be promising noninvasive biomarkers for BC detection.

Unlabelled: Background and rationale for the study. Continuing search for suitable tumor-markers is of clinical value in managing patients with various malignancies. These markers may be presented as intracellular substances in tissues or may be released into the circulation and appear in serum. Therefore, this work is concerned with identification and quantitative determination of epithelial membrane antigen (EMA) and fibronectin and estimating their performances as surrogate markers for identifying hepatocellular carcinoma (HCC)., Results: A total of 627 individuals constituted this study [fibrosis (F1-F3) = 217; cirrhosis = 191; HCC = 219]. Western-blot was used for identifying EMA and fibronectin in sera. As a result, a single immunoreactive band was shown at 130-kDa and 90-kDa corresponding to EMA and fibronectin, respectively. They were quantified using ELISA providing values in HCC higher than fibrosis or cirrhosis with a significant difference (P < 0.0001). For identifying HCC, EMA showed 0.82 area under receiver-operating characteristic curve (AUC) with sensitivity = 70% and specificity = 78% while fibronectin yielded AUC = 0.70 with sensitivity = 67% and specificity = 82%. FEBA-Test comprising fibronectin and EMA together with total-bilirubin and AFP was constructed yielding AUC = 0.92 for identifying HCC from cirrhosis with sensitivity = 89% and specificity = 85%. FEBA-Test was then tested for differentiating HCC from fibrosis showing AUC = 0.97 with sensitivity = 90% and specificity = 89%. FEBA-Test enabled the correct identification of HCC patients with CLIP 0-1 and size ≤ 3 cm with AUC = 0.80 and AUC = 0.84, respectively, indicating its ability in identifying early HCC., Conclusions: A four-marker index may improve the early detection of HCC with a high degree of accuracy.

Currently, the search for suitable hepatocellular carcinoma (HCC) biomarkers is very intensive. Besides, efficacy and cost/effectiveness of screening and surveillance of cirrhotics for the diagnosis of HCC is still debated. So, the present study is concerned with the evaluation of cytokeratin-1 (CK-1) and nuclear matrix protein-52 (NMP-52) for identifying HCC. Two-hundred and eighty individuals categorized into three groups [liver fibrosis (F1-F3), cirrhosis (F4), and HCC] constituted this study. Western blot was used for identifying CK-1 and NMP-52 in serum samples. As a result, a single immunoreactive band was shown at 67 and 52 kDa corresponding to CK-1 and NMP-52, respectively. Both CK-1 and NMP-52 bands were cut and electroeluted separately. These markers were quantified in sera using ELISA. Patients with HCC were associated with higher concentrations of CK-1 and NMP-52 than those without HCC with a significant difference (P < 0.0001). CK-1 showed an area under receiver-operating characteristic curve (AUC) of 0.83 with 75 % sensitivity and 82 % specificity while NMP-52 yielded 0.72 AUC with 62 % sensitivity and 70 % specificity for identifying HCC. HCC-DETECT comprising CK-1 and NMP-52 together with AFP was then constructed yielding 0.90 AUC for identifying HCC with 80 % sensitivity and 92 % specificity. HCC-DETECT was then tested for separating HCC from F1-F3 showing 0.94 AUC with 80 % sensitivity and 93 % specificity. In conclusion, CK-1 in conjunction with NMP-52 and AFP could have a potential role for improving the detection of HCC with a high degree of accuracy.

Background: Perinatal exposure to hepatitis C virus (HCV) antigens during pregnancy may affect the developing immune system in the fetus. We aimed to study the perinatal transmission of HCV structural and non-structural antigens., Methods: Sera from 402 pregnant mothers were tested for anti-HCV antibody and HCV RNA. HCV antigens were determined in sera from 101 HCV-infected mothers and their cord blood., Results: In both serum and cord blood samples, HCV NS4 (non-structural 4) at 27 kDa, E1 (envelope 1) at 38 kDa and E2 (envelope 2) at 40 kDa were identified, purified and quantified using western blotting, electroelution and ELISA. Maternal sera and neonate cord blood samples had similar detection rates for NS4 (94.1%), E1 (90.1%) and E2 (90.1%). The mean maternal serum levels (optical density, OD) of HCV NS4 (0.87 ± 0.01), E1 (0.86 ± 0.01) and E2 (0.85 ± 0.01) did not differ significantly (p > 0.05) from those of neonatal cord blood (0.83 ± 0.01, 0.87 ± 0.01 and 0.85 ± 0.01, respectively). Also, strong correlations (p < 0.0001) were shown between sera and cord blood sample levels of HCV NS4, r = 0.77; E1, r = 0.76 and E2, r = 0.80. The vertical transmission of these antigens in vaginal delivery did not differ significantly (p > 0.05) from those in caesarean section., Conclusions: These findings indicate that vertical transmission of HCV NS4, E1 and E2 antigens was very high. Thus, exposure to these antigens may influence the developing immune responses to natural infection or future vaccination.

Unlabelled: BACKGROUND AND RATIONALE FOR THE STUDY: The assessment of liver fibrosis provides useful information not only for diagnosis but also for therapeutic decision. This study was concerned with determining the levels of collagen III and its degrading enzyme matrix metalloproteinase-1 (MMP-1) as direct and complementary markers for liver fibrosis staging., Results: A total of 269 chronic hepatitis C patients constituted this study. Western blotting was used for identifying collagen III and MMP-1 in serum samples. As a result, collagen III and MMP-1 were identified, respectively, at 70 and 245 kDa using their respective mono-specific antibodies. These two markers were quantified in sera of patients using ELISA. Next, Fibro-check was constructed combining collagen III and MMP-1 together with other indirect markers which reflect alteration in hepatic functions that proved useful to stage liver fibrosis. Fibro-check produced area under the receiver-operating characteristic curve (AUC) 0.91 and 0.83 for significant (F2-F4) and cirrhosis (F4), respectively. Additionally, we estimated the performance of Fibro-check in comparison with aspartate to platelet ratio index (APRI) and fibrosis index. Fibro-check seems to be more efficient than both of them. Fibro-check was then applied to the validation study to test its accuracy and reproducibility showing AUCs 0.90 for F2-F4 and 0.86 for F4., Conclusions: Fibro-check combining 'direct' and 'indirect' markers using a mathematical formula may improve the staging of liver fibrosis with a high degree of accuracy and seems more efficient than APRI and Fibrosis index in this group of Egyptian patients.

Immunohistochemical studies proved that the presence of breast cancer (BrCa) is accompanied by elevated levels of epithelial membrane antigen (EMA) and decreased levels of cytokeratin-1 (CK1). We, therefore, hypothesize that the serum EMA/CK1 ratio may serve as a promising biomarker for early diagnosis of breast cancer. The circulating levels of EMA and CK1 were determined by Western blot and enzyme-linked immunosorbent assay (ELISA) in sera from 102 women with BrCa and 90 women as controls (40 with benign breast disease and 50 healthy). EMA at 130 kDa and CK1 at 67 kDa were identified, purified, and quantified in sera of BrCa patients using ELISA. EMA/CK1 ratio values were found to discriminate BrCa patients from controls (P < 0.0001) with high diagnostic ability (area under the curve [AUC] = 0.901, sensitivity = 82, specificity = 76). The sensitivity and specificity for early-stage (≤ T2) BrCa were 72 and 76%, respectively. The ratio values of patients with late-stage (>T2) tumors were significantly higher than those of patients with early-stage (≤ T2) tumors. Moreover, higher grades (grades 2-3) were associated with higher values than grade 1 tumors. AUC values in different BrCa patients who had early stage, low grade, or size ≤ 2 cm were 0.855, 0.762, and 0.839, respectively. AUC values of patients with positive lymph node or positive distant metastasis were 0.907 and 0.913, respectively. We show for the first time the impact of serum EMA and CK1 ratio in BrCa detection. Differential EMA/CK1 values may serve as a diagnostic marker in early-stage breast cancer patients.

Background: A simple scoring system is needed to discriminate HCC from patients with chronic liver diseases (CLD). The simplest score would be one that requires only variables that can be documented simply from routine laboratory tests without the need for sophisticated tests., Methods: Data from the estimation group (1351 patients) and the validation group (2208 patients) were retrospectively analysed. Liver fibrosis-negative control and liver cirrhosis were compared with HCC. Area under ROC curve (AUC) were used to develop HCC-α-fetoprotein-routine test (HCC-ART)., Results: Hepatocellular carcinoma-AFP-routine test showed diagnostic accuracy for liver cirrhosis vs HCC with ROC curves of 0.99%, sensitivity of 97%, and specificity of 96% in the estimation, and 0.95%, 90%, and 83%, respectively, in the validation. Sensitivity (97%) and specificity (100%) were obtained to discriminate HCC from liver fibrosis. Area under curve for AFP at 400 U l(-1) was 0.70, sensitivity was 41%, and specificity was 99% in the estimation, and 0.77%, 54%, and 99%, respectively, in the validation. The AUC for HCC-ART in HCC with single tumour, absent vascular invasion, size <2 cm and CLIP score (0-1) were 0.95, 0.93, 0.86, 0.87, respectively, compared with 0.72, 0.71, 0.71, 0.50, respectively, for AFP., Conclusion: Hepatocellular carcinoma-AFP-routine test could increase the accuracy of HCC screening and surveillances and could be used worldwide without extra efforts.

Background: Several noninvasive predictive models were developed to substitute liver biopsy for fibrosis assessment., Aim: To evaluate the diagnostic value of fibronectin which reflect extracellular matrix metabolism and standard liver functions tests which reflect alterations in hepatic functions., Material and Methods: Chronic hepatitis C (CHC) patients (n = 145) were evaluated using ROC curves and stepwise multivariate discriminant analysis (MDA) and was validated in 180 additional patients. Liver biochemical profile including transaminases, bilirubin, alkaline phosphatase, albumin, complete blood count were estimated. Fibronectin concentration was determined using monoclonal antibody and ELISA., Results: A novel index named fibronectin discriminant score (FDS) based on fibronectin, APRI and albumin was developed. FDS produced areas under ROC curves (AUC) of 0.91 for significant fibrosis and 0.81 for advanced fibrosis. The FDS correctly classified 79% of the significant liver fibrosis patients (F2-F4) with 87% sensitivity and 75% specificity. The relative risk [odds ratio (OR)] of having significant liver fibrosis using the cut-off values determined by ROC curve analyses were 6.1 for fibronectin, 4.9 for APRI, and 4.2 for albumin. FDS predicted liver fibrosis with an OR of 16.8 for significant fibrosis and 8.6 for advanced fibrosis. The FDS had similar AUC and OR in the validation group to the estimation group without statistically significant difference., Conclusion: FDS predicted liver fibrosis with high degree of accuracy, potentially decreasing the number of liver biopsy required.

Background and Study Aims: Non-invasive methods for the assessment of liver fibrosis are clinically important where hepatitis C virus (HCV) is common in Egypt. Our aim was to evaluate the diagnostic performance of a panel of simple blood markers of liver fibrosis in chronic hepatitis C (CHC) patients., Patients and Methods: A total of 199 patients with CHC evaluated for eligibility for antiviral therapy were included. Liver biochemical profile including transaminases, bilirubin, alkaline phosphatase, serum albumin, complete blood count prothrombin time and AFP were estimated. Liver biopsy was done. Statistical analyses were performed by logistic regression and receiver operating characteristic (ROC) curves to assess and compare diagnostic accuracy of blood markers. A stepwise combination algorithm was developed and validated prospectively in 135 additional patients., Results: α-Foetoprotein (AFP) was the most efficient marker among other markers tested. The areas under the curves (AUCs) of AFP were 0.77 for significant liver fibrosis (F2-F4), 0.75 for advanced liver fibrosis (F3-F4) and 0.76 for liver cirrhosis (F4). The stepwise multivariate discriminant analysis (MDA) selected a novel non-invasive index for discriminating patients with significant liver fibrosis, named Fibro-α score. Fibro-α score=(1.35 (numeric constant) +AFP (IUml(-1))×0.009584+aspartate aminotransferase (AST)/alanine aminotransferase (ALT)×0.243-platelet count (×10(9)l(-1))×0.001624). The Fibro-α score was used for patients with advanced liver fibrosis and liver cirrhosis. The AUCs of Fibro-α score were 0.82 for patients with advanced liver fibrosis and 0.80 for those with cirrhosis. These results were reproduced in a validation study with no significant difference., Conclusion: While liver biopsy is invasive, expensive and, in some settings, impossible to do, Fibro-α score is simple, cheap, non-invasive and may be useful for predicting significant liver fibrosis., (Copyright © 2011 Arab Journal of Gastroenterology. Published by Elsevier Ltd. All rights reserved.)

To study the interaction of the prohypertensive renin-angiotensin axis with the antihypertensive renal prostaglandins, angiotensin-converting enzyme inhibition (captopril and teprotide) and angiotensin blockade (Sar1-Ile8-AII) were produced in rabbits in vivo and renal slice prostaglandin E2 was measured in vitro after 30 minutes of incubation in Krebs-Ringer HCO3- buffer. In rabbits with angiotensin-converting enzyme inhibition, de novo prostaglandin E2 synthesis decreased in cortical, outer medullary and papillary slices by 85, 52 and 47 percent, respectively. Similar degrees of inhibition were observed with angiotensin blockade. It is concluded that renal prostaglandin E2 synthesis is angiotensin II dependent under these conditions. This finding suggests that any increase in the prohypertensive antinatriuretic renin-angiotensin axis may be associated with a secondary increase in renal prostaglandin E2 which may be acting in an antihypertensive natriuretic compensatory fashion.

Aspirin, salicylic acid and indomethacin reversibly inhibit prostaglandin binding to human serum proteins. This effect was demonstrated in the sera of normal subjects and of rheumatoid arthritis patients treated with aspirin as well as by addition of these drugs to serum in vitro. The displacement of serum prostaglandins by salicylate is likely to affect the kinetics of prostaglandin transport and may facilitate the delivery of prostaglandins from serum to tissue receptors.

To test the hypothesis that renal prostaglandin (PG) biosynthesis is regulated by angiotensin (AII), rabbits were given prolonged treatment with the AII analogue, Sar1-Ileu8AII (200 micrograms/kg/4 hr, subcutaneously), for 2 days during a low, normal, and high sodium intake. Sodium restriction augmented plasma renin activity (PRA), which was associated with a rise in basal renal PGE2 synthesis and urinary excretion, whereas sodium supplementation attenuated PRA with a decrease in renal PGE2 synthesis and urinary excretion. Sar1-Ileu8AII administration, with either a low, normal, or high salt intake, suppressed PRA. Sar1-Ileu8AII injection with a low sodium intake also suppressed renal PGE2 synthesis and excretion that was associated with a fall in blood pressure, suggesting an antagonistic action of this agent on vascular beds and renal PGE2 synthesis. On the other hand, with a high sodium intake Sar1-Ileu8-AII increased renal PGE2 synthesis and excretion as well as blood pressure, revealing an agonistic action of this compound under these conditions. The results suggest that exogenous AII analogue may act as an antagonist or agonist depending on sodium intake and endogenous AII levels, renal PGE2 synthesis is dependent on AII levels, either endogenously produced or exogenously administered (as an AII agonist), and the action of AII analogue on vascular beds and renal PGE2 synthesis does not appear to parallel its action on renin-AII feedback regulation at the juxtaglomerular cell especially under conditions of high sodium intake.

Immunoreactive prostaglandin E2 (PGE2) was measured in slices of renal papilla (P), outer medulla (OM), and cortex (C) before and after 30 min of incubation (biosynthesis) in Krebs-Ringer HCO3- buffer in rabbits on low (LS), normal (NS), and high (HS) sodium diets. The 24-h urine PGE2 was also measured daily for 10 days prior to incubation. Daily urine PGE2 was significantly higher (911 +/- 54 ng) in LS, decreasing to 605 +/- 33 at NS, and 558 +/- 48 ng at HS, Initial slice PGE2 was highest in P at LS (35.5 +/- 5.1 MICROGRAMS/G), 5.1 microgram/g), decreasing to 16.9 +/- 1.3 at NS and 18.0 +/- 2.6 micrograms/g at HS. Similar patterns were observed in OM and C, which were quantitatively much lower. PGE2 biosynthesis was highest at LS (P, 139 +/- 21; OM, 58.8 +/- 5.1; C, 0.20 +/- 0.05 micrograms.G-1.30 Min-1) and lowest at HS (P, 58.9 +/- 7.4; OM, 11.8 +/- 3.1; C, 0.07 +/- 0.01 micrograms.g-1.30 min-1). Although PGE2 concentration was higher in P than in OM, the percent increase in OM PGE2 biosynthesis on LS was 3--4 times greater than in P. Since OM is 28% and P is 2% of total renal mass, these results indicate that LS markedly stimulates PGE2 biosynthesis primarily in OM and to a lesser extent in P and C, findings suggesting an important role for OM PGE2 in the renal adaptation to sodium deprivation.

The effects of chronic alterations in dietary sodium intake on urinary prostaglandin (PG) E2 and thromboxane (TX) B2 was investigated in the rabbit. Sodium restriction, over a 15-day period, reduced daily urinary PGE2 and TXB2 in concordance with urinary flow (V) and sodium excretion (UNa+V), but increased plasma renin activity (PRA) and plasma aldosterone concentration (PAC). Sodium repletion, on the other hand, increased urinary PGE2 and TXB2 in proportion to the rise in V, but reduced PRA and PAC. During both sodium diets PGE2 and TXB2 correlated positively with V and negatively with PRA. It is concluded that chronic sodium intake produces opposite changes in the renal prostaglandin and the renin-angiotensin systems.

The effects of captopril on renal function and prostaglandin E2 excretion were investigated in rabbits undergoing chronic sodium depletion. Captopril administered for six days, via rate-controlled osmotic pumps, caused diuresis and marked natriuresis which were accompanied by a significant reduction of urinary prostaglandin E2 excretion and of glomerular filtration rate. It is concluded that captopril reduces the renal excretion of prostaglandin E2 and that its diuretic and natriuretic effects are prostaglandin E2-independent.

Experiments were performed to determine the influence of varying inspired oxygen tension on renal prostaglandin E2 (PGE2) excretion, renal hemodynamics, and water and electrolyte excretion in the conscious dog. Hypoxic exposure (PIO2 = 56 torr) resulted in a 13% increase in renal blood flow (RBF), while hyperoxic breathing with PIO2 of 700, 1426, or 2139 torr, all resulted in significant 5--7% decline in RBF, a response that was significantly attenuated compared to the striking renal vasoconstriction caused by hyperoxia in anesthetized dogs. Hyperbaric oxygenation (HBO) (1426 torr O2, 2139 torr O2) was associated with unexpected decreases in urine flow (V) of 61% and 70%, respectively. The antidiuresis and mild hemodynamic adjustments were correlated with a 67% decline in urinary PGE2 excretion (UPGE2 x V) when the dogs breathed 700 torr O2, while exposure to 1426 torr O2 and 2139 torr O2 diminished UPGE2 x V by 92% and 99%, respectively. Plasma antidiuretic hormone (ADH) concentration, measured during exposure to 1426 torr O2, was unchanged. In addition, this nonpharmacologic hyperbaric decline in PGE2 excretion was not associated with any changes in sodium excretion of renin secretion, in contrast to the usual depression of these variables with pharmacologic PG inhibition (indomethacin). The HBO antidiuresis may be a consequence of an increased medullary osmotic gradient secondary to reduced vasa recta blood flow. Alternatively, this antiduresis could occur as a consequence of a lowering of the normal functional antagonism existing between PGE2 and ADH, such that the influence of endogenous ADH is potentiated.

To test the hypothesis that renal PGs may mediate the renal functional defect of potassium depletion, rabbits were placed on normal potassium and potassium-deficient diets for 7 weeks, and measurements were made of urinary PGE2 excretion; renal cortical, medullary, and papillary PGE2 content; and in vitro, de novo PGE2 biosynthesis. In the sixth week maximal urinary osmolality declined significantly, from 1118 +/- 44 mOsm/kg of H2O in controls to 666 +/- 25 in potassium-deficient animals, accompanied by a corresponding decrease in urinary excretion of potassium from 12.2 +/- 0.7 mEq/24 hr to 0.93 +/- 0.1 and in muscle potassium content from 39.0 +/- 1.0 mEq/100 gm to 22.3 +/- 1.9. By 3 weeks urinary excretion of PGE2 was significantly lower in hypokalemic animals than in controls. Renal cortical, medullary, and papillary PGE2 tissue content decreased significantly, from 0.061 +/- 0.01 microgram/gm to 0.022 +/- 0.005, 0.73 +/- 0.09 microgram/gm to 0.267 +/- 0.036, and 8.6 +/- 1.04 microgram/gm to 4.6 +/- 1.4, respectively. In vitro PGE2 biosynthesis by cortical, medullary, and papillary slices from normal animals was 0.102 +/- 0.01, 9.55 +/- 1.7, and 25.5 +/- 2.8 microgram/gm/30 min, whereas corresponding values from hypokalemic rabbits were 0.04 +/- 0.006, 3.9 +/- 0.747, and 14.0 +/- 1.25 microgram/gm/30 min, respectively. These results indicate that renal slices from hypokalemic rabbits synthesize much less PGE2 in vitro than do normal controls. The date do not support the hypothesis that enhanced PGE2 synthesis mediates the renal concentrating defect of chronic potassium deficiency but suggest that decreased renal PGE2 production may underlie the impairment in renal hemodynamics known to exist in this condition.

The renal prostaglandins PGS2 and PGE2 possess potent antihypertensive and vasodepressor activity. The mechanism of blood pressure lowering effect is through peripheral arteriolar dilation with a fall in total peripheral resistance. PGA unlike PGE escape degradation by the lung and thus could circulate as antihypertensive hormones. Since plasma PGA levels rise in humans on a low sodium intake, it has been postulated that the beneficial effects of a low sodium diet in some hypertensives may be the result of an increase in peripheral vasodilating PGA. Support that plasma PGA may be a regulator of systemic blood pressure is also derived from the fact a PGA-secreting renal tumor was associated with a fall in blood pressure and a rise in plasma PGA in a previously hypertensive woman. The removal of the tumor resulted in a return of blood pressure to elevated levels and a concomitant fall in PGA. Recently, a number of human patients with essential hypertension have been infused with PGA1 and PGA2. It was observed that there was an initial increase in renal blood flow, sodium and water excretion which was associated with no change in the elevated blood pressure. When blood pressure ultimately fell, there was a return of renal blood flow, sodium and water excretion to preinfusion levels. It would appear that PGA compounds act as 'ideal' antihypertensive agents since they favorably effect renal resistance, sodium and water homeostasis, plasma volume, total peripheral resistance, blood pressure and indirectly cardiac output through baroreceptor stimulation, all factors known to be important in etiology in human hypertension.

Studies were conducted to investigate the interaction of renal prostaglandin E2 (PGE2) production and the renin-angiotensin system in the mechanism of furosemide-induced natriuresis. In conscious rabbits with permanent urinary bladder cannulation, furosemide in vivo (10 mg/kg) increased urinary water, sodium, and PGE2 excretion and plasma renin activity (PRA) over 50 min. Furosemide administered in vivo enhanced renal papillary but not cortical in vitro PGE2 biosynthesis. Prior administration of indomethacin at 2 mg/kg augmented the saluretic effect of furosemide, decreased its effect on UPGE2 V, abolished the rise in PRA, and reduced cortical but not papillary PGE2 biosynthesis. However, at 10 mg/kg, indomethacin reduced the saluretic effect of furosemide and eliminated the increase in UPGE2 V with continued suppression of PRA. Direct addition of furosemide in vitro to the incubation medium (10(-5) and 10(-3) M) markedly augmented papillary PGE2 synthesis. It is concluded that furosemide stimulates renal papillary PGE2 biosynthesis directly without mediation by angiotensin II, resulting in an increase in UPGE2 V, and the enhanced or inhibitory effect of indomethacin on furosemide-induced natriuresis is dose related and dependent on the degree of PGE2 synthesis inhibition in the presence of suppressed PRA, which occurred at all doses studied.

Since recent investigations have shown elevated urinary PGE2 and polyuria in hypokalemic animals which were reversed by PG synthesis inhibition with indomethacin, studies were undertaken to examine the effects of extracellular [K+] on renomedullary PG production in vitro. Slices of rabbit and human renal papilla were incubated in Krebs-Ringer HCO3- buffer, 95% O2-5% CO2, glucose 10 mM, HSA 4 gm/100 ml, for 30 min at 38 degrees C, with and without 1-14C-AA (10 micrometer). Measurments were made of total endogenous iPGE2 and iPGF2alpha production and radioactive AA leads to PGE2. In rabbit renal medulla values for iPGE2 (nmol/gm/30 min) were 252 +/- 20 at [K+] 0; 182 +/- 17 at [K+] 2.5 mEq/L; 163 +/- 18 at [K+] 5.5; and 129 +/- 17 [K+] 9.0 (p less than 0.005). iPGF2alpha was unaltered by changes in media potassium concentrations (6.8 +/- 0.9 nmol/gm/30 min at [K+] 0 and 6.2 +/- 0.8 at [K+] 9.0 MEq/L). In the human renal medulla iPGE2 was 9.5 +/- 1.6 nmol/gm/30 min at [K+] 0; 5.0 +/- 0.7 at [K+] 2.5 mEq/L; 5.3 +/- 0.3 at [K+] 5.5; and 4.6 +/- 1.0 at [K+] 9.0 (p less than 0.05). AA leads to PGE2 (nmol/gm/30 min) was 3.21 +/- 0.92 at [K+] 0; 2.47 +/- 0.57 at [K+] 2.5 mEq/L; 1.30 +/- 0.30 at [K+] 5.5; and 0.76 +/- 0.4 at [K+] 9.0 in rabbit medulla (P less than 0.005). It is postulated that direct stimulation of papillary PGE2 biosynthesis by low extracellular [K+] impairing the cAMP-generating response to vasopressin could represent the initial event in the pathogenesis of vasopressin-resistant polyuria.

Urinary PGE2 and PFG 2 alpha excretion (UPGV) were determined prior, during and after 48 h treatment with angiotensin-II-blocker, Sar1-Ile8-angiotensin II (200 microgram/kg/3 h), in rabbits maintained on chronic low (LS) or high (HS) salt diets. UPGE2V and F2 alpha were significantly (P < 0.001) higher in LS than in HS. Sar1-Ile-8-angiotensin II decreased the elevated UPGE2 V and UPGF2 alpha V in LS from 2.60 +/- 0.084 microgram/24 h to 1.13 +/- 0.21 microgram/24 h and from 6.63 +/- 0.61 to 3.77 +/- 0.86 microgram/24 h respectively. In animals with HS intake, angiotensin II blockade failed to effect urinary prostaglandin excretion.

The effects of verapamil on renal function, the renin-angiotensin-aldosterone system and renal prostaglandin E2 were investigated in the rabbit. Verapamil, administered with rate-controlled osmotic pumps, showed no significant effects on plasma renin activity, plasma aldosterone and urinary prostaglandin E2 excretion. There were marked rises in the glomerular filtration rate and calcium excretion but no significant change in slat and water excretion was observed with verapamil. It is concluded that the hypotensive response to verapamil is unrelated to the renin-angiotensin-aldosterone system and to renal prostaglandin E2.