Presence Of Kidney Research Articles

Anterior-To-Psoas Approach Measurements, Feasibility, Non-Neurological Structures at Risk and Influencing Factors: A Bilateral Analysis From L1-L5 Using Computed Tomography Imaging.

Spinal fusion through the anterior-to-psoas (ATP) technique harbors several approach-related risks. We used abdominal computed tomography imaging to analyze the L1-L5 ATP fusion approach measurements, feasibility, degree of obstruction by non-neurological structures, and the influence of patient characteristics on ATP approach dimensions. The vascular window, psoas window, safe window, and incision line anterior and posterior margins for the ATP approach were measured on abdominal computed tomography imaging. The feasibility of approach and the presence of kidneys, ribs, liver, spleen, and iliac crests within the ATP approach were also measured. Correlation and regression models among radiographic measurements and patient age, height, weight, and body mass index (BMI) were analyzed as well as differences in approach measurements based on sex. Safe window and incision line measurements were more accommodating for the left-sided vs right-sided ATP approach. At L4-5, the ATP approach was not feasible 18% of the time on the left side vs 60% of the time on the right side. The spleen was present 22%, 10%, and 3% of the time from L1-4, while the liver was present 56%, 30%, and 9% of the time. The iliac crests were not observed within ATP parameters. Patient age, height, weight, and BMI did not strongly correlate with approach measurements, although ATP dimensions did differ based on sex. This study reports characteristics of the ATP approach including approach measurements, feasibility, non-neurological structures at risk, and influencing factors to approach measurements. While incision line measurements are larger for male patients compared with female patients at the lower lumbar levels, safe window sizes are similar across all levels L1-L5. The kidneys, ribs, spleen, and liver are potential at-risk structures during the ATP approach, although the iliac crests pose limited concern for ATP technique. Patient characteristics such as age, height, weight, and BMI do not markedly affect ATP approach considerations.

Calcium oxalates among the minerals of Yakutia and in the human body

Oxalates, which are salts of oxalic acid, belong to a large group of organic minerals or biominerals that can occur both in the natural environment and inside living organisms, which makes them valuable for various sciences. We have discovered, for the first time, oxalates in several natural samples from the Daldynsky kimberlite field, the basin of the middle course of the Markha River, and the coastal outcrop on the Allah Yun River. We also confirmed their presence in kidney and gallbladder stone samples in the human body. X-ray phase analysis allowed us to establish the presence of weddellite or whewellite in association with quartz, dolomite, feldspar, mica, and chlorite in the samples under study. Meanwhile, the composition of the kidney stone in the human body represents a mixture of whewellite with uricite, the composition of the stone from the gallbladder includes uricite, whewellite, ammonium urate and brushite. Possible reasons for the formation of one- and two-in-one modifications of calcium oxalates in nature are also discussed. We conclude that these minerals are more widespread than previously assumed.

A rare case of KILT syndrome in Ireland: A case report

Venous thromboembolism (VTE), comprising deep vein thrombosis (DVT) and pulmonary embolism (PE), is associated with significant morbidity and mortality. Congenital absence of the inferior vena cava (IVC) is reported in current literature as a rare risk factor for DVT. The presence of kidney and IVC abnormalities on computed tomography together with lower limb thrombosis is collectively referred to as KILT syndrome (Kidney and IVC Abnormalities with Leg Thrombosis), an extremely rare cause of extensive bilateral lower limb DVT.We present a case of KILT syndrome, diagnosed for the first time after the age of 60 years and the first case reported in the Irish population. The patient presented to the emergency department with unilateral limb pain with a prior history of provoked DVT. Clinical gestalt, a high Wells Score, and raised D-Dimer strongly supported a diagnosis of DVT. Lower limb duplex ultrasound confirmed bilateral external iliac and femoral vein thrombus, with computed tomography venography revealing an absent infrarenal IVC and atrophy of the left kidney. The medical team subsequently admitted the patient for therapeutic anticoagulation and investigation. After review by haematology, the patient was discharged on an indefinite duration of anticoagulation with follow-up with our coagulation services. In any patient with bilateral lower limb DVT, comprehensive assessment and investigation, with particular emphasis on imaging, is imperative to exclude rare associated conditions.

Uptake and Survival Outcomes Following Immune Checkpoint Inhibitor Therapy Among Trial-Ineligible Patients With Advanced Solid Cancers

Immune checkpoint inhibitors (ICIs) are part of standard of care for patients with many advanced solid tumors. Patients with poor performance status or organ dysfunction are traditionally ineligible to partake in pivotal randomized clinical trials of ICIs. To assess ICI use and survival outcomes among patients with advanced cancers who are traditionally trial ineligible based on poor performance status or organ dysfunction. This retrospective cohort study was conducted in 280 predominantly community oncology practices in the US and included 34 131 patients (9318 [27.3%] trial ineligible) who initiated first-line systemic therapy from January 2014 through December 2019 for newly diagnosed metastatic or recurrent nontargetable non-small cell lung, urothelial cell, renal cell, or hepatocellular carcinoma. Data analysis was performed from December 1, 2019, to June 1, 2021. Trial ineligibility (Eastern Cooperative Oncology Group performance status ≥2 or the presence of kidney or liver dysfunction); first-line systemic therapy. The association between trial ineligibility and ICI monotherapy uptake was assessed using inverse probability-weighted (IPW) logistic regressions. The comparative survival outcomes following ICI and non-ICI therapy among trial-ineligible patients were assessed using treatment IPW survival analyses. Because we observed nonproportional hazards, we reported 12-month and 36-month restricted mean survival times (RMSTs) and time-varying hazard ratios (HRs) of less than 6 months and 6 months or greater. Among the overall cohort (n = 34 131), the median (IQR) age was 70 (62-77) years; 23 586 (69%) were White individuals, and 14 478 (42%) were women. Over the study period, the proportion of patients receiving ICI monotherapy increased from 0% to 30.2% among trial-ineligible patients and 0.1% to 19.4% among trial-eligible patients. Trial ineligibility was associated with increased ICI monotherapy use (IPW-adjusted odds ratio compared with non-ICI therapy, 1.8; 95% CI, 1.7-1.9). Among trial-ineligible patients, there were no overall survival differences between ICI monotherapy, ICI combination therapy, and non-ICI therapy at 12 months (RMST, 7.8 vs 7.7 vs 8.1 months) or 36 months (RMST, 15.0 vs 13.9 vs 14.4 months). Compared with non-ICI therapy, ICI monotherapy showed evidence of early harm (IPW-adjusted HR within 6 months, 1.2; 95% CI, 1.1-1.2) but late benefit (adjusted HR among patients who survived 6 months, 0.8; 95% CI, 0.7-0.8). In this cohort study, compared with trial-eligible patients, trial-ineligible patients with advanced cancers preferentially received first-line ICI therapy. A survival difference was not detected between ICI and non-ICI therapies among trial-ineligible patients. Positive results for ICI in phase 3 trials may not translate to this vulnerable population.

Experimental evidence of pathogenic role of IgG autoantibodies in IgA nephropathy.

IgA nephropathy is thought to be an autoimmune disease wherein galactose-deficient IgA1 (Gd-IgA1) is recognized by IgG autoantibodies, resulting in formation and renal accumulation of nephritogenic immune complexes. Although this hypothesis is supported by recent findings that, in renal immunodeposits of IgA nephropathy patients, IgG is enriched for Gd-IgA1-specific autoantibodies, experimental proof is still lacking. IgG isolated from sera of IgA nephropathy patients or produced as a recombinant IgG (rIgG) was mixed with human Gd-IgA1 to form immune complexes. IgG from healthy individuals served as a control. Nude and SCID mice were injected with human IgG and Gd-IgA1, in immune complexes or individually, and their presence in kidneys was ascertained by immunofluorescence. Pathologic changes in the glomeruli were evaluated by quantitative morphometry and exploratory transcriptomic profiling was performed by RNA-Seq. Immunodeficient mice injected with Gd-IgA1 mixed with IgG autoantibodies from patients with IgA nephropathy, but not Gd-IgA1 mixed with IgG from healthy individuals, displayed IgA, IgG, and mouse complement C3 glomerular deposits and mesangioproliferative glomerular injury with hematuria and proteinuria. Un-complexed Gd-IgA1 or IgG did not induce pathological changes. Moreover, Gd-IgA1-rIgG immune complexes injected into immunodeficient mice induced histopathological changes characteristic of human disease. Exploratory transcriptome profiling of mouse kidney tissues indicated that these immune complexes altered gene expression of multiple pathways, in concordance with the changes observed in kidney biopsies of patients with IgA nephropathy. This study provides the first in vivo evidence for a pathogenic role of IgG autoantibodies specific for Gd-IgA1 in the pathogenesis of IgA nephropathy.

Drug-induced atrioventricular blockages

Atrio-ventricular (AV) blockages are a serious violation ofthe heart rhythm. One of the reasons for the development ofthis pathology may be taking medications. This effect has asignificant number of drugs used for the treatment of diseasesof the cardiovascular system, central nervous system, generaland local anesthetics, antineoplastic drugs, and many others.The main mechanism for the development of drug-induced AVblockades is the inhibition of AV node conduction. The mostcommon risk factors for the development of drug-inducedAV blockades are taking two and more drugs that have aninhibitory effect on AV conduction, the initial duration of thePQ interval more than 0.2 second, initial dysfunction of the AVnode, increased plasma concentration of a potential inducerdrug due to the presence of kidney and/or liver disease, drugdrug interactions, and specific risk factors for individual drugs.Special attention in solving this problem should be paid to bothstopping the developed AV conduction disorder – medicationor using an electric cardiostimulator, and its prevention. Thisarticle systematizes the literature data on drug-induced AVblockades in order to increase the awareness of practitionersand patients about their prevalence, risk factors, approachesto diagnosis, treatment and prevention.

COVID-19 and Kidney Disease: Update on Epidemiology, Clinical Manifestations, Pathophysiology and Management.

Acute kidney injury (AKI) is relatively common in critically ill coronavirus disease 2019 (COVID-19) patients and it increases mortality and prolongs hospital stay. This article aimed to investigate the history, virology, epidemiology, clinical manifestations, pathophysiology and management of COVID-19 disease, in general, and the pathogenetic mechanisms of severe acute respiratory distress syndrome coronavirus 2 (SARS-CoV2)-induced kidney damage, in particular. Keywords like SARS-CoV2, COVID-19, renal impairment, sepsis, viremia, etc. were used to find relevant publications from PubMed, Scopus, Google Scholar, and clinical trials registry websites. According to different studies, kidney involvement in COVID-19 typically occurs in patients who develop acute respiratory distress syndrome (ARDS) or multiorgan failure. The kidney damage in COVID-19 has been shown to be multifactorial, involving direct viral infection, indirect injury by sepsis, hemodynamic alterations, cytokine storm, disseminated intravascular coagulation and other unknown mechanisms. The presence in kidney of angiotensin-converting enzyme 2 (ACE2), a receptor for the virus, has been proven, but few cases of direct viral presence in kidney tissue have been published. Therefore, further studies are needed to investigate the exact mechanisms underlying kidney impairment. Since the development of AKI is one of the important risk factors for mortality in COVID-19 patients, optimal management of AKI may improve the outcomes. Key Words: Acute kidney injury, Angiotensin-converting enzyme, Sepsis, Cytokine storm, Kidney replacement therapy, Coronavirus disease 2019.

Kidney and Tumor Segmentation using U-Net Deep Learning Model

Medical Image Segmentation is a challenging field in the area of Computer Vision. In this paper U-Net deep learning model was used for semantic segmentation. The reason for shortlisting U-Net was its suitability on small data set and also it was originally designed for Biomedical Image segmentation process. Visual representations of the predicted results have shown promising results using U-Net. Experimental results were computed on two different cases. Case No 1, includes testing the method on images for which labelled information was available and considering only those slices where the presence of kidney was detected. Case No 2, involves testing the method on those images who’s labelled information was not available and applying the method on all the CT slices with respect to a patient. Experimental results was based on a metric called IOU (Intersection over Union) score which is one of the most commonly used metric in semantic segmentation.

Renal involvement in paroxysmal nocturnal hemoglobinuria: an update on clinical features, pathophysiology and treatment

ABSTRACTObjectives: The present review summarizes the available knowledge regarding acute and chronic kidney dysfunction in patients with paroxysmal nocturnal hemoglobinuria (PNH) focusing on its clinical features, pathophysiology and treatment.Methods: A thorough PubMed search was performed using as main keywords: ‘paroxysmal nocturnal hemoglobinuria’, ‘acute kidney injury’, ‘chronic kidney disease’ and ‘eculizumab’.Results: PNH’s etiopathogenesis is based on acquired mutations that lead to the reduction or absence of CD55 and CD59 complement regulators, which are responsible for some of the disease’s major clinical features, like intravascular hemolysis, cytopenias and thrombosis. PNH is often underdiagnosed, mainly due to its occasional mild manifestations and to its ability to mimic other severe clinical conditions. Various mechanisms have been proposed for the kidney damage attributed to the release of cell-free heme and free iron, including inflammatory response, oxidative stress, nitric oxide depletion, renal ischemia, membrane damage and apoptosis. Eculizumab, a terminal complement inhibitor, provides a safe and effective treatment option, especially when it is initiated early in the presence of kidney damage.Discussion: Kidney injury is a poorly investigated clinical feature of PNH that affects a significant portion of patients. Increased awareness is needed by physicians to recognize the early signs and symptoms of acute and chronic renal insufficiency, so as to initiate the necessary therapy. It is also important to re-evaluation of PNH-specific treatments during the course of the disease.Conclusion: Understanding the difficult but at the same time impressive mechanisms behind PNH remains a challenge for treating physicians.

Peptide receptor radionuclide therapy in the management of gastrointestinal neuroendocrine tumors: efficacy profile, safety, and quality of life.

Peptide receptor radionuclide therapy (PRRT), developed over the last two decades, is carried out using radiopharmaceuticals such as 90Y-DOTA-Tyr3-octreotide and 177Lu-DOTA-Tyr3-octreotate (177Lu-Dotatate). These radiocompounds are obtained by labeling a synthetic somatostatin analog with a β-emitting radioisotope. The compounds differ from each other in terms of their energetic features (due to the radionuclide) and peptide receptor affinity (due to the analog) but share the common characteristic of binding specific membrane somatostatin receptors that are (generally) overexpressed in neuroendocrine neoplasms (NENs) and their metastases. NENs are tumors arising from diffuse neuroendocrine system cells that are classified according to grading based on Ki67 percentage values (Grades 1 and 2 are classed as neuroendocrine tumors [NETs]) and to the anatomical site of occurrence (in this paper, we only deal with gastroenteropancreatic [GEP]-NETs, which account for 60%–70% of all NENs). They are also characterized by specific symptoms such as diarrhea and flushing (30% of cases). Despite substantial experience gained in the area of PRRT and its demonstrable effects in terms of efficacy, safety, and improvement in quality of life, these compounds are still not registered (registration of 177Lu-Dotatate for the treatment of midgut NETs is expected soon). Thus, PRRT can only be used in experimental protocols. We provide an overview of the work of leading groups with wide-ranging experience and continuity in data publication in the area of GEP-NET PRRT and report our own personal experience of using different dosage schedules based on the presence of kidney and bone marrow risk factors. Our results on the retreatment of patients previously administered 90Y-DOTA-Tyr3-octreotide with a low dosage of 177Lu-Dotatate are also included. A comment on potential future developments of PRRT in GEP-NETs is provided.

Predictors of hospitalisations for heart failure and mortality in patients with pulmonary hypertension associated with left heart disease: a systematic review

ObjectivesLeft heart disease (LHD) is the main cause of pulmonary hypertension (PH), but little is known regarding the predictors of adverse outcome of PH associated with LHD (PH-LHD). We conducted...

Transgenic Expression of Human LAMA5 Suppresses Murine Lama5 mRNA and Laminin α5 Protein Deposition

Laminin α5 is required for kidney glomerular basement membrane (GBM) assembly, and mice with targeted deletions of the Lama5 gene fail to form glomeruli. As a tool to begin to understand factors regulating the expression of the LAMA5 gene, we generated transgenic mice carrying the human LAMA5 locus in a bacterial artificial chromosome. These mice deposited human laminin α5 protein into basement membranes in heart, liver, spleen and kidney. Here, we characterized two lines of transgenics; Line 13 expressed ∼6 times more LAMA5 than Line 25. Mice from both lines were healthy, and kidney function and morphology were normal. Examination of developing glomeruli from fetal LAMA5 transgenics showed that the human transgene was expressed at the correct stage of glomerular development, and deposited into the nascent GBM simultaneously with mouse laminin α5. Expression of human LAMA5 did not affect the timing of the mouse laminin α1–α5 isoform switch, or that for mouse laminin β1–β2. Immunoelectron microscopy showed that human laminin α5 originated in both glomerular endothelial cells and podocytes, known to be origins for mouse laminin α5 normally. Notably, in neonatal transgenics expressing the highest levels of human LAMA5, there was a striking reduction of mouse laminin α5 protein in kidney basement membranes compared to wildtype, and significantly lower levels of mouse Lama5 mRNA. This suggests the presence in kidney of a laminin expression monitor, which may be important for regulating the overall production of basement membrane protein.

OP23.10: The petrous part of the temporal bone as demonstrated by transvaginal ultrasound between 14 to 16 weeks of gestation

trophoblastic structure during first trimester. We wanted to know if kidney’s thickness estimation and if the position of umbilical arteries could help for this diagnosis. Methods: We tried to visualize by abdominal screening the echogenic capsule surrounding an hypoechogenic zone corresponding to adrenal gland and kidney. We compared the antero-posterior distance of this zone to the TAD for 500 1rst trimester normal screening with 2 cases of kidney agenesis. Then we tried to visualize the angle of the ombilical arteries separated or not by the bladder. Results: The capsule was seen in all cases at the condition to be perpendicular to its surface. Generally this measure corresponds to 25% of the TAD. Normally the volume of kidney and adrenal gland are equal but in case of kidney agenesis, adrenal gland takes all the place but as it’s volume is the same than normal, it’s 2 times less thin than normal. In our 2 cases of agenesis, the rate was 13%. Ombilical arteries could be seen in every case with an anterior way, at the condition of correct settings. Normal arteries are always non parallel even if the bladder is empty, but become parallel in case of agenesis. These differences are well demonstrated with color Doppler particularly in pour 2 cases of agenesis. Conclusions: Our study leads to think than kidney’s agenesis diagnosis could be done quite easily during the first trimester screening using the measurement of renal place’s thickness combined with the parallelism of the umbilical arteries. We think we could also affirm the presence of kidneys fetching these signs. We need still more cases of renal agenesis to prove it.

Influence of inherited and acquired thrombophilic defects on the clinical manifestations of mixed cryoglobulinaemia

To investigate the contribution of inherited and acquired thrombophilic defects to the clinical manifestations of mixed cryoglobulinaemia vasculitis. The following thrombophilic defects were investigated in 64 consecutive patients with HCV-associated mixed cryoglobulinaemia: aPLs, lupus anti-coagulant, homocysteinaemia, protein C and protein S concentrations, activated protein C resistance, plasminogen activator inhibitor-1 4G4G and 5G5G genotypes, and the presence of mutations of factor V (Leiden and H1299R), of prothrombin (G20210A) and of methyl tetrahydrofolate reductase (C677T and A1298C). Additional variables were demographic data, duration of the disease, cryocrit level and vascular risk factors (diabetes, hypertension, hypercholesterolaemia and smoking habit). The following clinical manifestations of mixed cryoglobulinaemia were analysed as dependent covariates: severity of purpura, presence of necrotic skin ulcers, presence of peripheral neuropathy and presence of kidney disease. Logistic regression analysis identified hyperhomocysteinaemia as a risk factor for severe purpura (P < 0.0001) and for the presence of skin ulcers (P < 0.0001), whereas none of the other thrombophilic defects influenced the clinical presentation of mixed cryoglobulinaemia. Purpura improved in two patients after lowering homocysteine with vitamin supplementation. Hyperhomocysteinaemia may be a risk factor for severe cutaneous manifestations in mixed cryoglobulinaemia.

Localization of formaldehyde production during frozen storage of European hake ( Merluccius merluccius )

The formation of dimethylamine and formaldehyde from trimethylamine N-oxide by the enzyme trimethylamine N-oxide demethylase in whole hake during frozen storage was studied. The objective was to check if there were parts of the muscle with a higher production of dimethylamine and formaldehyde, and if the presence of kidney during frozen storage had any significant influence on the production. Three variables were examined through one year storage. The first was anatomical location, considering the red muscle and three zones of white muscle, one located right over the kidneys, the dorsal part over the viscera, and the tail. The second variable was the temperature of storage, –11 °C or –18 °C. Finally, the influence of kidneys during storage, comparing fish with and without kidneys, was also evaluated.

Control of the translational efficiency of beta-F1-ATPase mRNA depends on the regulation of a protein that binds the 3' untranslated region of the mRNA.

The expression of the nucleus-encoded beta-F1-ATPase gene of oxidative phosphorylation is developmentally regulated in the liver at both the transcriptional and posttranscriptional levels. In this study we have analyzed the potential mechanisms that control the cytoplasmic expression of beta-F1-ATPase mRNA during liver development. Remarkably, a full-length 3' untranslated region (UTR) of the transcript is required for its efficient in vitro translation. When the 3' UTR of beta-F1-ATPase mRNA is placed downstream of a reporter construct, it functions as a translational enhancer. In vitro translation experiments with full-length beta-F1-ATPase mRNA and with a chimeric reporter construct containing the 3' UTR of beta-F1-ATPase mRNA suggested the existence of an inhibitor of beta-F1-ATPase mRNA translation in the fetal liver. Electrophoretic mobility shift assays and UV cross-linking experiments allowed the identification of an acutely regulated protein (3'betaFBP) of the liver that binds at the 3' UTR of beta-F1-ATPase mRNA. The developmental profile of 3'betaFBP parallels the reported changes in the translational efficiency of beta-F1-ATPase mRNA during development. Fractionation of fetal liver extracts revealed that the inhibitory activity of beta-F1-ATPase mRNA translation cofractionates with 3'-UTR band-shifting activity. Compared to other tissues of the adult rat, kidney and spleen extracts showed very high expression levels of 3'betaFBP. Translation of beta-F1-ATPase mRNA in the presence of kidney and spleen extracts further supported a translational inhibitory role for 3'betaFBP. Mapping experiments and a deletion mutant of the 3' UTR revealed that the cis-acting element for binding 3'betaFBP is located within a highly conserved region of the 3' UTR of mammalian beta-F1-ATPase mRNAs. Overall, we have identified a mechanism of translational control that regulates the rapid postnatal differentiation of liver mitochondria.

Purification from pig kidney of a microsomal cytochrome P 450 catalyzing 1α-hydroxylation of 25-hydroxyvitamin D 3

A cytochrome P 450 catalyzing 1α-hydroxylation of 25-hydroxyvitamin D 3 was purified from pig kidney microsomes. The enzyme preparation showed one protein band on gel electrophoresis with apparent M r of 52,500 and a specific cytochrome P 450 content of 10.7 nmol/mg of protein. The 25-hydroxyvitamin D 3 1α-hydroxylase copurified with the vitamin D 3 25-hydroxylase during purification. A cytochrome P 450 catalyzing 1α-hydroxylation was purified also from liver microsomes. The apparently homogeneous enzyme showed the same catalytic properties and apparent M r as the kidney enzyme. The results of the present communication demonstrate the presence in kidney of a previously unknown microsomal 1α-hydroxylase in addition to the assumed specific mitochondrial 1α-hydroxylase. The possibility that microsomal 1α-hydroxylation in pig kidney and liver is catalyzed by the previously described porcine microsomal vitamin D 25-hydroxylase(s) is discussed.

Evidence that human kidney produces a protein similar to lithostathine, the pancreatic inhibitor of CaCO3 crystal growth.

Pancreatic juice is supersaturated in calcium carbonate. CaCO3 crystal growth is controlled by lithostathine, a secretory protein synthesized by pancreatic acinar cells, first described as a constituent of pancreatic stones. It was recently reported that, in the thin descending limb of the Henle's loop, urine was supersaturated in CaCO3 (Coe FL, Parks JH: Defenses of an unstable compromise: crystallization inhibitors and the kidney's role in mineral regulation. Kidney Int. 1990: 38, 625-631. This observation suggested the presence in kidney of a similar inhibitor. In this study, we show that a protein immunologically related to lithostathine is actually present in urine of healthy subjects and in renal stones. Immunocytochemistry of kidney sections localized the protein to cells of the proximal tubules and thick ascending limbs of the Henle's loops. Protein extracts of renal stones inhibited CaCO3 crystal growth in vitro and this inhibition was significantly lifted by incubating the extracts with antibodies to lithostathine. The protein is not immunologically related to nephrocalcin. Because of its structural and functional similarities with pancreatic lithostathine, it was called renal lithostathine.

Remarks on the screening of antibiotics for antibacterial activity

The general principles of screening antibiotics for antimicrobial activity are similar to those for screening for other pharmacological effects. The system should be adapted to the specific character of the test substance and the objectives of the program. In the screening of beta-lactams, standard tests, such as determination of the MICs, effects of inoculum size or activity against systemic infection in mice, should be supplemented by less conventional studies on for instance activity against dormant bacteria or, in the case of penems or carbapenems, stability in the presence of kidney and lung dehydropeptidases.

Effect of tissue specificity of brain soluble fractions on Na+, K+-ATPase activity

Previous evidence from this laboratory indicated that catecholamines and brain endogenous factors modulate Na+,K(+)-ATPase activity of the synaptosomal membranes. The filtration of a brain total soluble fraction through Sephadex G-50 permitted the separation of two fractions -peaks I and II-which stimulated and inhibited Na+,K(+)-ATPase, respectively (Rodríguez de Lores Arnaiz and Antonelli de Gomez de Lima, Neurochem. Res. 11, 1986, 933). In order to study tissue specificity a rat kidney total soluble was fractionated in Sephadex G-50 and kidney peak I and II fractions were separated; as control, a total soluble fraction prepared from rat cerebral cortex was also processed. The UV absorbance profile of the kidney total soluble showed two zones and was similar to the profile of the brain total soluble. Synaptosomal membranes Na+,K(+)- and Mg2(+)-ATPases were stimulated 60-100% in the presence of kidney and cerebral cortex peak I; Na+,K(+)-ATPase was inhibited 35-65% by kidney peak II and 60-80% by brain peak II. Mg2(+)-ATPase activity was not modified by peak II fractions. ATPases activity of a kidney crude microsomal fraction was not modified by kidney peak I or brain peak II, and was slightly increased by kidney peak II or brain peak I. Kidney purified Na+,K(+)-ATPase was increased 16-20% by brain peak I and II fractions. These findings indicate that modulatory factors of ATPase activity are not exclusive to the brain. On the contrary, there might be tissue specificity with respect to the enzyme source.