CT imaging patterns of paraduodenal pancreatitis: a unique clinicoradiological entity.

AIM: To analyse the computed tomography (CT) findings of paraduodenal pancreatitis (PP) in patients treated at Amrita Institute of Medical Sciences. MATERIALS AND METHODS: Clinical, laboratory, and CT findings of 30 patients with PP treated from July 2007 to December 2020 were reviewed retrospectively. RESULTS: The average age of the patients was 45.9 years (19-60 years), which included 29 (96.7%) men, and 90% had a history of alcohol abuse. The majority [22 (73.3%)] presented with recurrent abdominal pain. Serum amylase was elevated in 21 (70%) patients and serum lipase was elevated in 25 (83.3%) patients. Carbohydrate antigen (CA 19-9) was elevated in three (10%) patients. The cystic pattern was seen in three (10%), solid pattern in 13 (43.3%), and solid-cystic pattern in 14 (46.7%) patients. The pure form of the disease was seen in seven (23.3%) patients, whereas the segmental form was seen in 23 (76.7%) patients. Descending duodenal wall thickening and enhancement was seen in 25 (83.3%) and 18 (60%) patients, respectively. The gastroduodenal artery was displaced medially in 12 (40%) patients and encased in five (16.7%) patients; however, it was not occluded in any of the patients. Calcifications were seen in the groove lesion in nine (30%) patients. The pancreas showed atrophic changes in 14 (46.6%) patients and calcifications in 12 (40%) patients. Distal common bile duct strictures were seen in three (10%) patients. CONCLUSIONS: The presence of sheet-like soft-tissue thickening in the groove with diffuse duodenal thickening and intramural/paraduodenal cysts are highly suggestive of PP. Identifying characteristic imaging findings of PP may help in prospective diagnosis and lead to conservative management of most of these patients avoiding unnecessary invasive procedures.

Insights into genetic diversity and population structure of Indian carrot (Daucus carota L.) accessions.

Carrot (Daucus carota L.) is acknowledged as a highly valuable vegetable crop. Despite having high demand, limited breeding efforts have been made to develop the varieties and hybrids suitable to wider climatic conditions due to improper characterization of the available germplasm. An accession panel (AP) consisting of 144 accessions of five different root colors representing Asiatic and Western gene pools collected from different parts of India was utilized in the present study. This diverse AP was used to assess the population structure and genetic diversity from 80 polymorphic DNA markers distributed throughout the genome. Population structure, neighbor-joining (NJ) tree, and principal coordinate analysis (PCoA)-based diversity assessment divided the AP into three subpopulations/clusters. Greater than ninety percent polymorphism and the higher average polymorphic information content (͂> 0.50) coupled with higher gene diversity (He) indicating the broad genetic base of the population. Moderate to high Fst and gene flow (Nm) between the subpopulations revealed a moderate genetic differentiation among Indian carrot accessions owing to the highly outcrossing nature of carrot. Analysis of molecular variance (AMOVA) exhibited higher variation among individuals within the subpopulations (69.00%) or total populations (19.00%) than among the subpopulations (13%) as expected in the single Daucus species used here. The information obtained in the study would benefit the carrot breeders to explore the genetic diversity of the Indian carrots in the carrot breeding program for widening the genetic base and multi-color target trait improvement.

Application of hot melt extrusion for improving bioavailability of artemisinin a thermolabile drug.

Hot melt extrusion has been used to produce a solid dispersion of the thermolabile drug artemisinin. Formulation and process conditions were optimized prior to evaluation of dissolution and biopharmaceutical performance. Soluplus®, a low Tg amphiphilic polymer especially designed for solid dispersions enabled melt extrusion at 110 °C although some drug-polymer incompatibility was observed. Addition of 5% citric acid as a pH modifier was found to suppress the degradation. The area under plasma concentration time curve (AUC0-24h) and peak plasma concentration (Cmax) were four times higher for the modified solid dispersion compared to that of pure artemisinin.

Study of prevalence of nonalcoholic fatty liver disease (NAFLD) in type 2 diabetes patients in India (SPRINT).

Non-alcoholic fatty liver disease (NAFLD) is a distinct hepatic condition and one of the most common causes of chronic liver disease globally. Prevalence of the disease is estimated to be around 9-32% in the general Indian population, with a higher incidence rate amongst obese and diabetic patients. We conducted this study to determine frequency and risk factors of NAFLD in nonalcoholic Indian type 2 diabetic (T2DM) patients, based on elevated aminotransferase levels, defined as per NHANES III criteria. Out of 924 patients (355 female/569 male), in age group of 25-84 years, enrolled at 189 centers across 101 cities in India, a cohort of 522(56.5%) T2DM patients were identified as having NAFLD. Prevalence of the disease was found to be higher in females (60%) than in males (54.3%) T2DM patients; with prevalence of NAFLD varying from 44.1% in western India to 72.4% in northern states. In our study the prevalence of NAFLD increased with increasing age, with 239(45.8%) identified patients in age group of 25-50 years and 283(54.2%) among those aged 51 years (OR:0.71, 95%CI: 0.54-0.92, p=0.005); with highest prevalence recorded in 61-70 year age group, at 61.8%. The results from the study reinforced the well established clinical association of NAFLD with elements of metabolic syndrome (MetS) including dyslipidemia, hypertension and obesity; as T2DM population with these co-morbid conditions had 38%, 17% and 14% higher risk respectively, for NAFLD. The mean AST and ALT levels were 54.8+/-36.1 IU/L and 55.6+/-39.8 IU/L, respectively in NAFLD population and highest in age group of 25-40 years and lowest in 71-84 years age group. Mean ALT levels were found to be higher than mean AST levels across all age groups in identified T2DM NAFLD cohort, with 340(65.3%) patients having elevation of both AST and ALT levels. The results from this study besides demonstrating the prevalence pattern of NAFLD and associated risk factors in Indian T2DM patients, also point out that even mild elevation in aminotransferase levels warrants attention, since it might more often than not point to previously unsuspected liver disease.

Aminoclay: a permselective matrix to stabilize copper nanoparticles.

Air sensitive copper nanoparticles have been stabilized using a water soluble aminoclay matrix. The aminoclay shows remarkable permselective behaviour allowing only the ionic species to diffuse through it and react with copper nanoparticles. It blocks the neutral molecule oxygen, thereby stabilizing the copper nanoparticles against oxidation for a longer period.

Congestive heart failure in a male with "carcinoma tongue": a case of mistaken identity.

We present a case of primary amyloidosis with macroglossia and restrictive cardiomopathy, that was mistakenly diagnosed as carcinoma of the tongue. He had characteristic echocardiographic findings, and bone marrow plasmacytosis but with normal serum electrophoresis and no Bence Jones proteins in the urine.

Valproate- and aminophylline-induced 'wet dog shakes'--a function of dose and time.

The time course of appearance of 'wet dot shakes' (WDS) was examined following valproic acid (VPA, 100, 200, 300, 400 mg/kg i.p.) and aminophylline (AMP, 50, 100, 150 mg/kg i.p.) injections. VPA and AMP at various doses showed a qualitative difference in their ability to induce WDS with no difference in intensity, confirming 'all or none' nature of the phenomenon. There was a significant (p<0.001), dose-dependent increase in the number of whole body shakes following first three doses of VPA but not after the administration of its highest dose (400 mg/kg). In contrast, the numbers of WDS produced by AMP were inversely proportional to its increasing doses. The maximum numbers of WDS were observed at 300 mg/kg of VPA and 50 mg/kg of AMP, within 10 min and 20-30 min during 1 h and 1 h 30 min observation period, respectively. The present stereotyped behavior induced by acute, single dose administration of VPA and AMP in non-toxic doses, being a reproducible phenomenon, lasting for a brief period may be anticipated to serve as a tool to explore mechanisms underlying WDS.

Influence of caffeine on pharmacokinetic profile of sodium valproate and carbamazepine in normal human volunteers.

The present study evaluates effect of pharmacokinetic interaction between caffeine (300 mg) in three divided doses with sodium valproate (400 mg) and carbamazepine (200 mg) given as single doses, in normal human volunteers, using a open cross over design. Both the serum concentration of sodium valproate and pharmacokinetic parameters remained unaltered, as against significant reduction in plasma concentration and area under the concentration curve of carbamazepine following the coadministration of caffeine. Also, the plasma t 1/2 (of carbamazepine was prolonged by two folds and bioavailability reduced by about 32% in presence of caffeine. The results are of clinical significance as xanthine consumption may have to be restricted in patients on carbamazepine therapy and this aspect may need further investigation.

Influence of adenosine, dipyridamole, adenosine antagonists and antiepileptic drugs on EEG after discharge following cortical stimulation.

The effects of adenosine (100 nM, icv), dipyridamole (DPM, 5 mg/kg, i.p.), adenosine A1 receptor antagonist 8-cyclopentyl-theophylline (8-CPT, 10 mg/kg, i.p.), and aminophylline (AMP) and caffeine (CAF) (at equivalent doses of 35 mg/kg, i.p.), were examined in rats. Anti-epileptic drugs (AEDs) were also administered i.p., viz, carbamazepine (CBZ, 10 mg/kg); phenobarbitone (PB, 10 mg/kg); phenytoin (PHT, 20 mg/kg); valproic acid (VPA, 300 mg/kg); and diazepam (DZP, 10 mg/kg), to study their effects on EEG after discharge (AD) and postictal depression (PID) induced by cortical stimulation. The AD parameters: (1) duration of EEG-AD (sec) and (2) number of spikes was noted both during pre and post drug treatment sessions. Adenosine and DPM had no special effects on AD parameters but showed significant prolongation of PID. All the adenosine antagonists, 8-CPT, AMP and CAF produced significant prolongation of AD duration, increase in number of spikes and reduced the duration of PID to a significant extent. Interestingly, some of the AEDs, viz. CBZ, VPA and DZP showed abolition of all the EEG-AD parameters whereas PB and PHT failed to show any significant effect. The results confirm previous findings on involvement of adenosine in postictal events.

Time course of action of three adenosine A1 receptor agonists with differing lipophilicity in rats: comparison of pharmacokinetic, haemodynamic and EEG effects.

In this study we investigated the relationship between the pharmacokinetics and the cardiovascular and electroencephalogram (EEG) effects of three adenosine agonists with differing lipophilicity. Conscious normotensive rats received either 600 microg/kg N6-(p-sulphophenyl) adenosine (SPA), 200 microg/kg N6-cyclopentyladenosine (CPA) or 600 microg/kg 1-deaza-2-chloro-N6-cyclopentyladenosine (DCCA) in a 5-min intravenous infusion. Changes in haemodynamics and EEG were monitored in conjunction with arterial blood sampling to determine blood concentrations of the compounds. The three adenosine agonists showed large differences in pharmacokinetic properties, resulting in terminal half-lives of 66 +/- 10, 8.2 +/- 0.4 and 24 +/- 1 min (mean +/- SEM) for SPA, CPA, and DCCA respectively. SPA had a significantly lower blood clearance relative to CPA and DCCA, whereas DCCA had the largest volume of distribution and degree of plasma protein binding. The relationship between concentration and heart rate could be described adequately by the sigmoidal Emax model. For SPA, CPA, and DCCA the EC50 values based on free drug concentrations were 423 +/- 92, 1.8 +/- 0.4 and 9.5 +/- 1.1 nM respectively. These in vivo values correlated closely with the affinity of the compounds for the adenosine A1 receptor as determined in radioligand binding studies, with corresponding Ki values of 1410 +/- 220, 4.7 +/- 0.6 and 102 +/- 74 nM (mean +/- SEM) respectively. In the EEG, only CPA produced a small decrease in the amplitude of beta waves. This study demonstrates that the three adenosine analogues have large differences in pharmacokinetics, which complicates comparison of their cardiovascular and central responses simply on the basis of dose. The application of an integrated PK/PD approach permits estimates of potency and activity which are independent of underlying dose and pharmacokinetics.

Aminophylline alters pharmacokinetics of carbamazepine but not that of sodium valproate--a single dose pharmacokinetic study in human volunteers.

Pharmacokinetic interaction of aminophylline with single dose sodium valproate (400 mg) and carbamazepine (200 mg) was evaluated in normal healthy volunteers using a cross over design. Neither the serum concentrations nor the pharmacokinetic parameters of sodium valproate (SV) were altered by the coadministration of aminophylline (AMP). In contrast AMP significantly decreased the plasma concentrations of carbamazepine (CBZ). The Cmax of CBZ was significantly lowered from 1.73 +/- 0.18 to 0.94 +/- 0.08 microgram/ml and the AUC o-t was significantly decreased from 76.19 +/- 6.20 to 52.66 +/- 1.84 micrograms/h/ml (P < 0.05). The pharmacokinetic parameters of CBZ that were altered in the presence of AMP were: the Tmax and t1/2 which was prolonged about threefold from 5.60 +/- 1.60 to 16.80 +/- 7.94 h and 44.88 +/- 4.50 to 125.07 +/- 29.09 h, respectively. The Vd was marginally increased from 2.19 +/- 0.13 to 3.85 +/- 0.57 L/kg and the Cl was decreased from 34.07 +/- 3.78 to 25.26 +/- 5.15 mL/min. None of these alterations are statistically significant. Bioavailability of CBZ was reduced by 29% in the presence of AMP, while that of SV was increased by about 8%. Results are of clinical significance because simultaneous administration of CBZ and AMP may reduce the efficacy of CBZ in epileptic patients.

An inexpensive method for fabrication of intracerebroventricular cannulae for rats.

An inexpensive and simple method to fabricate intracerebroventricular (i.c.v.) cannulae for rats with readily available material is described here. The procedure is cost effective and quick. The cannulae thus designed are suitable for injecting minute quantities (microliters) of drugs/chemicals interacerebroventricularly for acute or chronic experiments in rats.

Involvement of adenosine in postictal events in rats given electroshock.

The effect of a selective adenosine antagonist, 8-cyclopentyl 1,3-dimethylxanthine (8-CPT) was used to examine involvement of adenosine in ictal and postictal events in rats subjected to maximal electroshock (MES). MES induces the ictal event of hindlimb tonic extension (HLTE) followed by postictal depression (PID). 8-CPT 10 mg/kg, ip produced maximal significant reduction of PID without affecting HLTE, further confirming involvement of adenosine in PID. Carbamazepine and sodium valproate were studied independently and were coadministered with 8-CPT to determine if their anticonvulsant activity was modulated by adenosine and if they altered PID. 8-CPT did not antagonize the seizure protection afforded by CBZ or SV. CBZ significantly reduced postictal events whereas SV had no significant effect. These observations further confirm a role for adenosine in postictal phenomena.

Reverse single radial immunodiffusion for estimation of titre of anti IgG antibody.

Reverse Single Radial Immunodiffusion (SRID) for estimating titre of anti IgG antisera is reported. Unlike the conventional radial immunodiffusion, the antigen (IgG) is held immobile in the gel while the antibody (Anti IgG) diffuses radially from the well (7 microliters) and the diameter of the resulting immuneprecipitates after immunodiffusion at 4 degrees C for 24 hr, represents a linear correlation with the antibody titre. The procedure was standardised by an extensive trial and error employing different concentrations of human IgG in the gel (60-240 micrograms) against varying dilutions of the standard antibody (titre: 3.8 mg/ml). The best results were obtained at 80 micrograms of IgG in the gel. The locally raised rabbit anti IgG antisera displayed a distinctive titre pattern under optimised conditions. Technical reproducibility, high-sensitivity threshold (0.25 mg/ml), simultaneous visual scrutiny of several antibody batches at a glance and ability to assess the shelf life of the stored antisera are its distinct assets.

Inhibition of Salmonella ferlac by enterobacteria under in-vitro conditions.

Interactions of Proteus morganii, Proteus mirabilis, Proteus sp. Klebsiella oxaenae and Serratia marcescens isolated from vegetable salads of mass feeding systems with Salmonella ferlac (a new subgenus VI of Salmonella) isolated from a hostel cook's hands and lizard droppings were recorded following in-vitro nephelometric analysis. Nephelometric analysis revealed inhibition of S. ferlac by all the tested isolates from fifth hour of mixed culture interaction. K. oxaenae was the strong inhibitor.

Antiepileptic drugs delay the onset of seizures induced by aminophylline in conscious rats.

Aminophylline, 285.7 +/- 2.19 mg/kg infused intravenously in unanaesthetized rats produced onset of seizures within 3.2 +/- 0.99 minutes. Seizures were repetitive and death occurred in 10.5 +/- 1.75 minutes. Pretreatment of rats with carbamazepine, sodium valproate and diazepam at doses that prevented electroshock induced seizures were effective in significantly postponing seizures and death, but did not reduce mortality. Concomitant EEG studies in aminophylline infused rats showed that cortical excitability evidenced by initial cortical spiking occurred at 42 secs and polyspiking at 165 seconds. Following diazepam, the initial cortical spike was delayed 50 fold, appearing after 36 minutes. Antiepileptic drugs and EEG monitoring may prove useful in patients with status asthmaticus receiving intravenous aminophylline.

Influence of adenosine receptor antagonists, aminophylline and caffeine, on seizure protective ability of antiepileptic drugs in rats.

Interaction of methylxanthines, aminophylline (AMP) and caffeine (CAF) on seizure protective ability of various antiepileptic drugs (AEDs), diphenylhydantoin (DPH), phenobarbitone (PB), diazepam (DZP), sodium valproate (SV) and ethosuximide (ESM) was investigated in rats. In the maximal electroshock seizure (MES) test, ED100 doses (mg/kg, ip), against hind limb tonic extension (HLTE) were DPH, 20; PB, 10; DZP, 10 and SV, 300. The interaction of AEDs with AMP (100 mg/kg, ip) reduced the seizure protection afforded by DPH, PB and DZP to 20%, while the efficacy of SV remained unimpaired. Interaction with CAF (200 mg/kg, ip) abolished the seizure protection by DPH and DZP, reduced that by PB to 20%, while the protective effect of SV was unchanged. In pentylenetetrazole (PTZ, 70 mg/kg, sc) induced seizure test, ED100 doses (mg/kg, ip) against clonic convulsions were PB, 10; DZP, 1; SV, 300 and ESM, 200. Complete seizure protection against clonic convulsions following SV or ESM was not significantly influenced by either AMP or CAF, whereas the protective effect of PB and DZP was reversed. SV and ESM showed a qualitative departure in their anti-seizure activity profiles following interaction with either AMP or CAF when compared with the other AEDs.

End stage renal disease serum contains a specific renal cell growth factor.

End stage renal disease (ESRD) kidneys display abnormal growth characterized by a continuum of cystic disease, adenoma and carcinoma. This study evaluates the hypothesis that serum of patients with ESRD contains increased amounts of a growth factor which specifically induces proliferation of renal cells. ESRD sera compared to sera from normal controls induced a two to three-fold increase in the proliferative rate of renal cell carcinoma cell lines and normal kidney explants compared to cell lines from other sites. The increased proliferative activity of ESRD sera on renal cells was paralleled by an increase in cytosolic free calcium. The growth factor activity was encoded by a polypeptide of between 15 and 30 kd. The activity of ESRD sera on renal cells was not mimicked or inhibited by epidermal growth factor, basic fibroblast growth factor and platelet derived growth factor indicating that the renal cell specific growth factor activity in ESRD is different from these factors.

Inhibition of anticonvulsant action of carbamazepine by aminophylline and caffeine in rats.

Interaction of two well known methyl xanthines, aminophylline--an antiasthmatic agent--and caffeine--commonly present in beverages, on the seizure protective ability of carbamazepine (CBZ) against electrically and chemically induced seizures in rats was investigated. Aminophylline (75 mg/kg, ip) did not alter the activity of CBZ (10 mg/kg, ip; ED100) on maximal electroshock seizures while dose dependent antagonism of CBZ efficacy was seen at 100 and 150 mg/kg, ip. Similar effects were observed with caffeine (200 and 250 mg/kg, ip). At the highest tolerated doses, aminophylline (150 mg/kg, ip) and caffeine (250 mg/kg, ip) produced antagonism of CBZ protection against pentylenetetrazole seizures. These observations support the possibility that the antagonism due to the interaction of these drugs could be related to their action at adenosine receptor sites in the brain.