Decreased atrial natriuretic factor receptors and impaired cGMP generation in glomeruli from the cardiomyopathic hamster

To determine a possible basis for the decreased action of atrial natriuretic factors (ANF) in congestive heart failure, we compared the cardiomyopathic hamster (CMH) in frank congestive failure, and the age-matched, normal, F1B strain of Golden Syrian Hamsters. Scatchard analysis of competitive binding studies revealed two classes of glomerular receptors. The CMH exhibited decreased binding overall and a markedly decreased number of high affinity receptors but comparable receptor affinity compared to the F1B. In contrast, the low affinity receptor population in the CMH had a much greater affinity compared to the F1B while receptor number was similar. Plasma ANF levels were substantially elevated in the CMH compared to the F1B and in-vitro generation of cGMP was significantly lower in the CMH. Such abnormalities could contribute to the resistance to ANF in this disease.     

Characterization and physiologic regulation of atrial natriuretic factor receptors in rabbit preglomerular renal microvessels.

There has been no direct demonstration of the presence of guanylate cyclase-linked atrial natriuretic factor receptors in renal preglomerular microvasculature. Using [125I]ANF, we have demonstrated the presence of high affinity (Kd = 80 pM) and low affinity (Kd = 7.2 nM) ANF receptors in membranes derived from rabbit renal preglomerular microvessels (afferent arterioles and interlobular arteries). These microvessels also exhibited the presence of particulate bound ANF-sensitive guanylate cyclase. The density of the high affinity ANF receptor in desoxycorticosterone-treated rabbits on a high-salt diet (31 +/- 3 fmol/mg protein) was nearly half of that seen in rabbits on a normal diet (53 +/- 4 fmol/mg protein; p less than 0.01, n = 4). Data from this study demonstrated the presence of renal preglomerular ANF receptors and suggested that these receptors (perhaps in addition to glomerular ANF receptors) may participate in the regulation of extracellular volume.     

Structural studies on the specific capsular polysaccharide from Rhizobium trifolii, TA-1

The repeating unit of the specific capsular polysaccharide from the bacterium Rhizobium trifolii (TA)-1 has been shown to contain (a) terminal 4,6-O-(1-carboxyethylidene)-D-galactose (1 residue), (b) (1 → 3)-linked 4,6-O-(1-carboxyethylidene)-D-glucose (1 residue), (c) (1 → 4)-(1 → 6)-linked D-glucose (1 residue), (d) (1 → 4)-linked D-glucuronic acid (1 residue), and (e) (1 → 4)-linked D-glucose (4 residues). The pyruvylated sugars were shown to be positioned sequentially, and at least one other unit was interposed between them and the branch point.     

An extensive review on antifungal approaches in the treatment of mucormycosis

During the period of COVID-19, the occurrences of mucormycosis in immunocompromised patients have increased significantly. Mucormycosis (black fungus) is a rare and rapidly progressing fungal infection associated with high mortality and morbidity in India as well as globally. The causative agents for this infection are collectively called mucoromycetes which are the members of the order Mucorales. The diagnosis of the infection needs to be performed as soon as the occurrence of clinical symptoms which differs with types of Mucorales infection. Imaging techniques magnetic resonance imaging or computed tomography scan, culture testing, and microscopy are the approaches for the diagnosis. After the diagnosis of the infection is confirmed, rapid action is needed for the treatment in the form of antifungal therapy or surgery depending upon the severity of the infection. Delaying in treatment declines the chances of survival. In antifungal therapy, there are two approaches first-line therapy (monotherapy) and combination therapy. Amphotericin B ( 1 ) and isavuconazole ( 2 ) are the drugs of choice for first-line therapy in the treatment of mucormycosis. Salvage therapy with posaconazole ( 3 ) and deferasirox ( 4 ) is another approach for patients who are not responsible for any other therapy. Adjunctive therapy is also used in the treatment of mucormycosis along with first-line therapy, which involves hyperbaric oxygen and cytokine therapy. There are some drugs like VT-1161 ( 5 ) and APX001A ( 6 ), Colistin, SCH 42427, and PC1244 that are under clinical trials. Despite all these approaches, none can be 100% successful in giving results. Therefore, new medications with favorable or little side effects are required for the treatment of mucormycosis.     

Leaf architecture of some acanthaceae

Leaf architectural pattern has been studied in 27 genera and 35 species of the Acanthaceae. The major venation pattern conforms to pinnate camptodromous with eucamptodromous or festooned brochidodromous secondaries, pinnate craspedodromous inAcanthus ilicifolius and acrodromous inLepidagathis trinervis. Intersecondary veins are common. The marginal ultimate venation is looped. The areoles are variable in size. The vein endings are usually simple, linear or cuved or divide once or twice dichotomously. Isolated vein endings, tracheids, isolated free vein endings and extension cells are observed. Transfusion tracheids are seen inDicliptera verticillata. Miniature vessel elements with simple perforation plates are noticed lying free in the areole or at the end of tracheids inSeriocalyx scaber andThunbergia grandiflora.Elytraria acaulis, Nelsonia canescens andStaurogynae zeylanica exhibit venation pattern shown by majority of the taxa studied, of the Acanthaceae.     

Mechanism of increased renal prostaglandin E2 in uranyl nitrate-induced acute renal failure

We have previously demonstrated that decreased cortical prostaglandin metabolism can contribute significantly to an increase in renal tissue levels and activity of prostaglandin E₂ in bilateral ureteral obstruction, a model of acute renal failure. In the present study, we have further investigated whether alterations in prostaglandin metabolism can occur in a nephrotoxic model of acute renal failure. Prostaglandin synthesis, prostaglandin E₂ metabolism (measured as both prostaglandin E₂-9-ketoreductase and prostaglandin E₂-15-hydroxydehydrogenase activity), and tissue concentration of prostaglandin E₂ were determined in rabbit kidneys following an intravenous administration of uranyl nitrate (5 mg/kg). No changes in the rates of cortical microsomal prostaglandin E₂ and prostaglandin F_2α synthesis were noted at the end of 1 and 3 days, while medullary synthesis of prostaglandin E₂ fell by 47% after 1 day and 43% after 3 days. Cortical cytosolic prostaglandin E₂-9-ketoreductase activity was found to be decreased by 36% and 76% after 1 and 3 days respectively. No significant changes were noted in cortical cytosolic prostaglandin E₂-15-hydroxydehydrogenase activity after 3 days. Cortical tissue levels of prostaglandin E₂ increased by 500% at the end of 3 days. These data demonstrate that in nephrotoxic acute renal failure, decreased prostaglandin metabolism (i.e., prostaglandin E₂-9-ketoreductase activity) can result in increased tissue levels of prostaglandin E₂ in the absence of increased prostaglandin synthesis and suggest that alterations in prostaglandin metabolism may be an important regulator of prostaglandin activity in acute renal failure.     

Biochemical evidence for PGI2 and PGE2 receptors in the rabbit renal preglomerular microvasculature

It has been proposed that a portion of the biologic actions of vasodilator prostaglandins occurs via an interaction with specific adenylate cyclase-linked receptors. This hypothesis was explored further in the renal microvasculature by examining the effects of PGI2, PGE1, and PGE2 on rabbit preglomerular microvascular adenylate cyclase. A membrane preparation derived from freshly isolated rabbit renal preglomerular microvessels was used in these studies. NaF, forskolin, or 5'-guanylyl imidodiphosphate were found to be effective in increasing adenylate cyclase activity in the absence of exogenous guanosine-5'-triphosphate. A dose-dependent stimulation of adenylate cyclase was also observed with guanosine-5'-triphosphate. PGE1, PGE2, and PGI2 produced a dose-dependent stimulation of adenylate cyclase activity only in the presence of guanosine-5'-triphosphate suggesting that this nucleotide is essential for prostaglandin-induced stimulation of the enzyme. PGI2 exhibited a time-dependent increase in adenylate cyclase activity and this increased activity reached a plateau at 20-25 min. When PGE1 and PGE2 were added together, no additive effect on adenylate cyclase stimulation was noted whereas PGI2 and PGE2 when added together produced an additive stimulatory effect. When viewed together, these data suggest the presence of separate PGI2 and PGE adenylate cyclase-linked receptors in rabbit renal preglomerular microvessels. These findings also suggest that in the renal microvasculature, cyclic AMP may be a second messenger mediating the vasodilatory effects of both PGI2 and PGE2.     

Enhanced Orai1-mediated store-operated Ca2+ channel/calpain signaling contributes to high glucose-induced podocyte injury

Podocyte injury induced by hyperglycemia is the main cause of kidney dysfunction in diabetic nephropathy. However, the underlying mechanism is unclear. Store-operated Ca²⁺ entry (SOCE) regulates a diversity of cellular processes in a variety of cell types. Calpain, a Ca²⁺-dependent cysteine protease, was recently shown to be involved in podocyte injury. In the present study, we sought to determine whether increased SOCE contributed to high glucose (HG)–induced podocyte injury through activation of the calpain pathway. In cultured human podocytes, whole-cell patch clamp indicated the presence of functional store-operated Ca²⁺ channels, which are composed of Orai1 proteins and mediate SOCE. Western blots showed that HG treatment increased the protein abundance of Orai1 in a dose-dependent manner. Consistently, calcium imaging experiments revealed that SOCE was significantly enhanced in podocytes following HG treatment. Furthermore, HG treatment caused overt podocyte F-actin disorganization as well as a significant decrease in nephrin protein abundance, both of which are indications of podocyte injury. These podocyte injury responses were significantly blunted by both pharmacological inhibition of Orai1 using the small molecule inhibitor BTP2 or by genetic deletion of Orai1 using CRISPR-Cas9 lentivirus. Moreover, activation of SOCE by thapsigargin, an inhibitor of Ca²⁺ pump on the endoplasmic/sarcoplasmic reticulum membrane, significantly increased the activity of calpain, which was inhibited by BTP2. Finally, the calpain-1/calpain-2 inhibitor calpeptin significantly blunted the nephrin protein reduction induced by HG treatment. Taken together, our results suggest that enhanced signaling via an Orai1/SOCE/Calpain axis contributes to HG-induced podocyte injury.     

Comparing Accuracy of Wrist Intra-articular Needle Placement Via Ulnocarpal Approach by Training Level: A Cadaveric Study

BackgroundIntra-articular injections are a standard therapy and diagnostic tool for a variety of wrist conditions. Accurate needle placement is crucial for proper therapeutic benefit and prevention of complications. While some studies claim accurate needle placement requires imaging, others conclude that anatomical guidance is sufficient. This study aimed to evaluate the accuracy of intra-articular wrist needle placement with the ulnocarpal approach across differing levels of training using clinical anatomy alone.MethodsFourteen fresh-frozen, above-elbow cadaveric specimens were used. Intra-articular needle placement into the wrist via an ulnocarpal approach was attempted by nine study participants: two interns, two junior-level residents, two senior-level residents, two hand fellows, and one attending hand surgeon. Each injection was performed based on clinical examination and landmarks alone. The number of attempts and total time taken for each injection was recorded.ResultsOverall success rate was 71%, (89 of 126 attempts) and did not vary significantly across levels of training. Average time for needle placement among all participants was 10.9 ± 6.5 seconds. Timing of successful intra-articular needle placement (10.4 ± 5.2 seconds) significantly differed between levels. However, timing did not trend in any direction with more or less training. No significant difference was noted in total attempts or attempts with successful outcomes when comparing level of training.ConclusionThe ulnocarpal approach is a viable option for injection or aspiration of the wrist without image guidance. We were unable to show any relevant trends with timing or number of attempts in comparison to level of training. Level of Evidence: V     

Natural host-range and experimental transmission of Laem-Singh virus (LSNV)

Slow growth caused by viral diseases has become a major constraint in shrimp aquaculture. Laem-Singh virus (LSNV), a positive-sense single-stranded RNA (ssRNA) virus, has been identified in Penaeus monodon showing slow growth syndrome. To examine the host-range and transmission modes of the virus, 6 species of penaeid shrimp of varying life stages, sourced from the wild and from farms, as well as juvenile mud crabs Scylla serrata, were screened using RT-nested PCR. LSNV was detected in P. monodon, Fenneropenaeus merguiensis, Metapenaeus dobsoni, and Litopenaeus vannamei, but not in E indicus, Marsupenaeus japonicus or S. serrata. LSNV was most prevalent in P. monodon followed by M. dobsoni, F. merguiensis, and L. vannamei, and real-time quantitative RT-PCR (qRT-PCR) showed that LSNV infection loads were highest in P. monodon, followed by L. vannamei, M. dobsoni, and E merguiensis. The nucleotide sequence of the LSNV RdRP gene fragment amplified by RT-nested PCR was highly conserved (99% identity) across these 4 penaeid species. LSNV was detected in both small and normal-sized P. monodon collected from the same pond. In experimental infections of both P. monodon and S. serrata, LSNV infection loads increased over time. The present study extends the known natural penaeid host-range and geographical distribution of LSNV and shows for the first time the potential susceptibility of S. serrata.