Distribution and risk factors of postoperative endophthalmitis in people with diabetes

Purpose:To evaluate (i) the distribution of postoperative endophthalmitis (POE) in patients who underwent cataract surgery, (ii) risk factors in diabetic versus nondiabetic patients, and (iii) distribution of POE in those who had undergone rapid reduction of preoperative blood sugar levels versus those with normal blood sugar levels.Methods:Medical records were reviewed from January 1995 to July 2021. In total, 391 eyes of 391 patients who developed POE after cataract surgery were studied. Patients with POE were divided into Group A, patients with diabetes (n = 128), and Group B, patients without diabetes (n = 263), and the associations of various clinical factors in the two groups were studied. Patients with diabetes with raised random blood sugars (RBS) preoperatively were subjected to a rapid reduction of blood sugar (RBS <200 mg%) to be considered eligible for surgery. Microbiological profile of patients was examined.Results:The cumulative incidence of POE over 26 years was 0.09%. Those who underwent a rapid reduction in preoperative blood sugar levels had higher rates of POE (53.1%) compared with (46.9%) those with blood sugar levels under control (P = 0.486). Men with diabetes had 1.634 times higher odds of POE (P = 0.048), and those with diabetes and hypertension had 3.961 times greater odds of having POE (P < 0.001) when adjusted for age, alcohol, smoking, and socioeconomic strata and presence of posterior capsule rupture. Positive culture results were observed in 45/128 (35%) patients with diabetes and 71/263 (27%) patients without diabetes. Staphylococcus epidermidis was the most commonly identified organism and was detected in 10/45 (22%) in those with diabetes and 21/71 (29%) in those without diabetes of all the culture-positive cases.Conclusion:In patients with POE, the odds are greater for men with diabetes, those with a history of hypertension, as well as those who undergo a rapid reduction of preoperative blood sugar.     

Antidiabetic and antioxidant potentials of spent turmeric oleoresin,a by-product from curcumin production industry

ObjectiveTo investigate the antidiabetic and antioxidant activity of spent turmeric oleoresin (STO).MethodsAntidiabetic activity of STO evaluated by α-amylase and α-glucosidase enzyme inhibition assays. The antioxidant capacity studied by DPPH., ABTS., superoxide radical scavenging and metal chelating activity methods.ResultsThe STO showed good antidiabetic activity by inhibiting key enzymes linked to type 2 diabetes, viz α-glucosidase and α-amylase with an IC50values of 0.71 and 0.16μg/mL respectively. The IC₅₀values for DPPH. and ABTS. assay were 58.1 and 33 μg/mL respectively. STO effectively scavenged the superoxide free radical with an IC50 value of 61.5μg/mL and showed a moderate iron chelation property.ConclusionsThe above study reveals that the spent turmeric oleoresin being wasted at present can be used as antioxidant and antidiabetic agent in food and neutraceutical products.     

New selective inhibitors of calcium-activated chloride channels … T16Ainh-A01, CaCCinh-A01 and MONNA … what do they inhibit?

Background and Purpose

T16A_inh-A01, CaCC_inh-A01 and MONNA are identified as selective inhibitors of the TMEM16A calcium-activated chloride channel (CaCC). The aim of this study was to examine the chloride-specificity of these compounds on isolated resistance arteries in the presence and absence (±) of extracellular chloride.

Experimental Approach

Isolated resistance arteries were maintained in a myograph and tension recorded, in some instances combined with microelectrode impalement for membrane potential measurements or intracellular calcium monitoring using fura-2. Voltage-dependent calcium currents (VDCC) were measured in A7r5 cells with voltage-clamp electrophysiology using barium as a charge carrier.

Key Results

Rodent arteries preconstricted with noradrenaline or U46619 were concentration-dependently relaxed by T16A_inh-A01 (0.1–10 μM): IC₅₀ and maximum relaxation were equivalent in ±chloride (30 min aspartate substitution) and the T16A_inh-A01-induced vasorelaxation ±chloride were accompanied by membrane hyperpolarization and lowering of intracellular calcium. However, agonist concentration–response curves ±chloride, with 10 μM T16A_inh-A01 present, achieved similar maximum constrictions although agonist-sensitivity decreased. Contractions induced by elevated extracellular potassium were concentration-dependently relaxed by T16A_inh-A01 ±chloride. Moreover, T16A_inh-A01 inhibited VDCCs in A7r5 cells in a concentration-dependent manner. CaCC_inh-A01 and MONNA (0.1–10 μM) induced vasorelaxation ±chloride and both compounds lowered maximum contractility. MONNA, 10 μM, induced substantial membrane hyperpolarization under resting conditions.

Conclusions and Implications

T16A_inh-A01, CaCC_inh-A01 and MONNA concentration-dependently relax rodent resistance arteries, but an equivalent vasorelaxation occurs when the transmembrane chloride gradient is abolished with an impermeant anion. These compounds therefore display poor selectivity for TMEM16A and inhibition of CaCC in vascular tissue in the concentration range that inhibits the isolated conductance.     

Reversible “Pulvinar sign” in Wernicke's encephalopathy

Young onset dementia is a challenge. We describe a case, where a patient presented with psychosis, dementia and MRI showing pulvinar sign, all of this typical of variant Cruetzfelt Jacob disease (CJD). Subsequent investigations lead to the diagnosis of a treatable illness and patient was improved and MRI sign reversed, underlining again the importance of search needed for treatable diseases in any “typical” case of fatal illness.     

Metaphyseal growth arrest lines in psychosocial short stature

Metaphyseal growth arrest lines are seen in children who experience significant physical stress such as infection or malnutrition over a sufficient period of time. These lines have not been reported previously in children with psychosocial short stature (PSS). Two boys and a girl with PSS with metaphyseal growth arrest lines on skeletal radiographs at the time of maximal stress in their homes are described. All three had reversible growth hormone insufficiency during admission, which is pathognomic for PSS. Multiple growth arrest lines in the distal end of the radius or vertebrae should alert clinicians to an alternative diagnosis in a child with growth hormone insufficiency. This may provide a clue to the diagnosis of occult PSS.     

TMEM16A knockdown abrogates two different Ca2+-activated Cl− currents and contractility of smooth muscle in rat mesenteric small arteries

The presence of Ca²⁺-activated Cl^? channels (CaCCs) in vascular smooth muscle cells (SMCs) is well established. Their molecular identity is, however, elusive. Two distinct Ca²⁺-activated Cl^? currents (I _Cl(Ca)) were previously characterized in SMCs. We have shown that the cGMP-dependent I _Cl(Ca) depends on bestrophin expression, while the “classical” I _Cl(Ca) is not. Downregulation of bestrophins did not affect arterial contraction but inhibited the rhythmic contractions, vasomotion. In this study, we have used in vivo siRNA transfection of rat mesenteric small arteries to investigate the role of a putative CaCC, TMEM16A. Isometric force, [Ca²⁺]_i, and SMC membrane potential were measured in isolated arterial segments. I _Cl(Ca) and GTPγS-induced nonselective cation current were measured in isolated SMCs. Downregulation of TMEM16A resulted in inhibition of both the cGMP-dependent I _Cl(Ca) and the “classical” I _Cl(Ca) in SMCs. TMEM16A downregulation also reduced expression of bestrophins. TMEM16A downregulation suppressed vasomotion both in vivo and in vitro. Downregulation of TMEM16A reduced agonist (noradrenaline and vasopressin) and K⁺-induced contractions. In accordance with the depolarizing role of CaCCs, TMEM16A downregulation suppressed agonist-induced depolarization and elevation in [Ca²⁺]_i. Surprisingly, K⁺-induced depolarization was unchanged but Ca²⁺ entry was reduced. We suggested that this is due to reduced expression of the L-type Ca²⁺ channels, as observed at the mRNA level. Thus, the importance of TMEM16A for contraction is, at least in part, independent from membrane potential. This study demonstrates the significance of TMEM16A for two SMCs I _Cl(Ca) and vascular function and suggests an interaction between TMEM16A and L-type Ca²⁺ channels.     

Recurrent parotitis

(1) Recurrent parotitis is probably caused by a congenital abnormality of the salivary gland ducts with recurrent attacks of ascending infection, perhaps aided by dehydration. The parotid gland is predominantly affected probably because of its lower rate of secretion compared with the submandibular gland. (2) The condition mainly affects children between the ages of 3 and 6, with males being more commonly affected. The symptoms peak in the first year of school, and usually, but not invariably, begin to subside at puberty. By the age of 22, most patients are completely symptom-free. When the disease starts after puberty, females are predominantly affected. (3) Ultrasound is the appropriate initial investigation, and is usually supplemented by sialography. The sialography may itself cause a resolution of symptoms. (4) Treatment is conservative in the first instance, and an expectant policy is indicated. More aggressive treatment is justified only for those adults with persistent problems. This may be parotid duct ligation, parotidectomy, or tympanic neurectomy, depending upon the preference and experience of the treating physician.     

Vasomotion has chloride-dependency in rat mesenteric small arteries

The possibility that Ca²⁺-activated Cl⁻ conductances (CaCCs) contribute to oscillations in vascular tone (vasomotion) is tested in isolated mesenteric small arteries from rats where cGMP independent (I _Cl(Ca)) and cGMP-dependent (I _Cl(Ca,cGMP)) chloride conductances are important. The effect of anion substitution and Cl⁻ channel blockers on noradrenaline (NA)-stimulated tension in isometrically mounted mesenteric arteries and for chloride conductance of smooth muscle cells isolated from these arteries were assessed electrophysiologically. Cl⁻ _o replacement with aspartate blocked vasomotion while 36mM SCN⁻ _o (substituted for Cl⁻) was sufficient to inhibit vasomotion. Oscillations in tone, membrane potential, and [Ca²⁺]_i disappeared with 36mM SCN⁻. DIDS and Zn²⁺ blocked I _Cl(Ca,cGMP) but not I _Cl(Ca). Vasomotion was not sensitive to DIDS and Zn²⁺, and DIDS and Zn²⁺ induce vasomotion in arteries without endothelium. The vasomotion in the presence of DIDS and Zn²⁺ was sensitive to 36mM SCN⁻ _o. The anion substitution data indicate that Cl⁻ is crucial for the V _m and [Ca²⁺]_i oscillations underlying vasomotion. The Cl⁻ channel blocker data are consistent with both CaCCs being important.