COVID-19 vaccination effectiveness: a review in early vaccine adopters in Asian Countries.

COVID-19 vaccines were designed to stimulate an immunological response, producing neutralizing antibodies against the SARS-CoV-2 spike protein. Vaccine variants such as mRNA, viral vector, whole-cell inactivated virus, and protein subunit vaccines, have been reported to be efficacious in phase III trials and have gained emergency use approval in many countries. However, several adverse effects are reported in certain types of vaccines. All vaccines are being expedited by some Asian countries as part of their national immunization programs. This review primarily discussed the selected manufacturers of the COVID-19 vaccines used and their effectiveness in early-adopting Asian countries. The effectiveness in reducing the infection rate and safety of COVID-19 vaccines in Japan, Thailand, Singapore and Malaysia was also analyzed based on the available data. Strategies that can be used to speed up the vaccination rate in reducing the number of COVID-19 cases were also evaluated.

Bioactivity-Guided Isolation and Identification of Anti-adipogenic Constituents from the n-Butanol Fraction of Cissus quadrangularis.

Obesity is marked by the buildup of fat in adipose tissue that increases body weight and the risk of many associated health problems, including diabetes and cardiovascular disease. Treatment options for obesity are limited, and available medications have many side effects. Thus there is a great need to find alternative medicines for treating obesity. This study explores the anti-adipogenic potential of the n-butanol fraction of Cissus quadrangularis (CQ-B) on 3T3-L1 mouse preadipocyte cell line. The expression of various lipogenic marker genes such as adiponectin, peroxisome proliferator-activated receptor gamma, leptin, fatty acid-binding proteins, sterol regulatory element-binding proteins, fetal alcohol syndrome, steroyl-CoA desaturase-1, lipoproteins, acetyl-CoA carboxylase alpha, and acetyl-CoA carboxylase beta were variously significantly downregulated. After establishing the anti-adipogenic potential of CQ-B, it was fractionated to isolate anti-adipogenic compounds. We observed significant reduction in neutral lipid content of differentiated cells treated with various fractions of CQ-B. Gas chromatography-mass spectrometry analysis revealed the presence of thirteen compounds with reported anti-adipogenic activities. Further studies to purify these compounds can offer efficacious and viable treatment options for obesity and related complications.

Differential response of the primate HPG axis to N-methyl-D, L-aspartate, but not to Kisspeptin challenge under euglycemic and hypoglycemic conditions.

Hypoglycemia inhibits the hypothalamic-pituitary-gonadal (HPG) axis by still incompletely deciphered mechanisms. Many evidences suggest that the hypoglycemia-induced inhibition of the HPG axis involves alteration of the hypothalamic gonadotropin-releasing hormone (GnRH) release, but neuroendocrine factors responsible for this alteration are yet to be completely elucidated. The current study was carried out to ascertain whether insulin-induced hypoglycemic suppression of the HPG axis involves modulation of responsiveness of the GnRH neuron to kisspeptin and excitatory amino acids (EAA) drives. Five intact chair-restraint habituated adult male rhesus monkeys (Macaca mulatta) were given intravenous boli of GnRH, hCG, human kisspeptin-10 (KP10), NMDA (N-methyl-D, L-aspartate, an EAA analogue), and vehicle in both insulin (1 IU/kg)-induced hypoglycemic (IIH) and normal euglycemic conditions. Specific RIAs were used for measuring plasma cortisol and T concentrations. KP10 and NMDA administration stimulated significantly (p<0.005) T secretion in both euglycemic and hypoglycemic monkeys. Mean post-KP10 T concentrations and AUC were comparable between euglycemic and hypoglycemic monkeys. However, mean post-NMDA T levels and AUC in hypoglycemic animals were significantly lower (p<0.01-0.005) as compared to the corresponding values in euglycemic animals. T response to GnRH and hCG was similar between hypoglycemic and euglycemic monkeys. Vehicle did not affect plasma T concentrations in all conditions. Our results demonstrate that while the primate HPG axis response to kisspeptin stimulation remains intact that to EAA excitation is attenuated in hypoglycemic conditions, suggesting that hypogonadism in IIH is contributed, in part, by reduced sensitivity of the GnRH neurons to EAA signaling in the primate hypothalamus.

Stemness gene expression profile of human adipose derived stem cells in long-term culture.

It is crucial to know whether stem cells retain its stemnness properties after advance in vitro manipulation. The objective of this study was to investigate the stemness gene expression of human adipose tissue derived stem cells (ADSCs) in long-term culture using quantitative RT-PCR technique. Our data showed that the expression level of Sox-2, Rex-1, FGF-4, Nanog, Nestin, BST-1, FZD-9 and Oct-4 were decreased gradually in long-term culture. This could mean that the ability of ADSCs to differentiate into other cell lineages reduce after extensive culture.

Discovery of new etchants for CR-39 detector.

After reporting the excellent etching properties of molten Ba(OH)2 8H2O as an etchant, we now report some more new and efficient etchants for CR-39 detector. CR-39 detectors were irradiated with fission fragments and alpha particles with a thin 252Cf source. The irradiated detectors were etched in a number of our newly introduced etching solutions as well as in conventionally used 6 M NaOH at 70 degrees C. The newly prepared etching solutions included NaOH/ethanol and NaOH/1-propanol. Processing conditions were optimized for these etchants. From fission and alpha track diameters, bulk etching velocity (VB), track etching velocity (VT), etching efficiency (eta) and their activation energies were determined and compared with that obtained for 6M NaOH at 70 degrees C.

Efficacy of extracorporeal shock wave lithotripsy for solitary lower calyceal stone: a statistical model.

OBJECTIVE: To evaluate the effect of inferior calyceal radiographic anatomy, number of extracorporeal shock wave lithotripsy (ESWL) sessions and stone size on the successful clearance of solitary inferior calyceal calculi after ESWL. PATIENTS AND METHODS: In a prospective study between January 2001 and November 2002, 66 renal units with a solitary inferior calyceal calculus of < or = 2 cm were treated with electrohydraulic ESWL. The infundibulopelvic angle (two definitions), infundibulovertebral angle, inferior calyceal infundibular diameter, infundibular length, cortical thickness over the lower pole, number of minor calyces and stone size were determined from intravenous urography before treatment. The number of ESWL sessions was also included in the analysis. Treatments which produced residual fragments not clearing within 3 months of satisfactory fragmentation were considered as failures. All patients in whom the treatment failed were treated successfully by percutaneous nephrolithotomy. The data were then analysed using two different statistical methods; first by intravariable differences using the test of proportion (Fisher's test) and then all the variables together using logistic regression. RESULTS: At 3 months 78.8% of the renal units were clear of stone. All intravariable differences were statistically significant except stone size (<1 cm, 1-2 cm). In a multivariate analysis of all variables, only stone size was the most important predictor for successful stone clearance (P = 0.03). CONCLUSIONS: ESWL is the initial treatment of choice in selected patients with inferior calyceal stones. The stone size appears to be the most important predictor for stone clearance.

Endopyelotomy in poorly functioning kidney: is it worthwhile?

BACKGROUND: Endopyelotomy is a minimally invasive surgical alternative for primary ureteropelvic junction (UPJ) obstruction. However, its success in poorly functioning kidneys is controversial. PATIENTS AND METHODS: In this retrospective study, 34 endopyelotomies performed on poorly functioning kidneys between January 1993 and December 1997 were reviewed. Of these, 13 patients had a glomerular filtration rate (GFR) <15 mL/min (Group I) and 21 had a GFR of 15 to 25 mL/min (Group II). All the patients insisted on endopyelotomy to avoid open surgery. Antegrade endopyelotomy was performed by the twin guidewire rail technique with a cold knife. An indwelling stent was kept for 2 to 6 weeks. Patients were followed up with assessment of symptoms and diuretic renograms at 3, 6, and 12 months postoperatively. RESULTS: Endopyelotomy was considered successful in 8 of 13 patients (62%) in Group I. Success was achieved in 19 of 21 patients (90%) in Group II. CONCLUSION: Endopyelotomy can be performed for improvement of symptoms. Stabilization or improvement in GFR is less pronounced in poorly functioning kidneys with primary UPJ obstruction.

Modified bulbar urethral sling procedure for the treatment of male sphincteric incontinence.

BACKGROUND AND PURPOSE: Urinary incontinence secondary to intrinsic sphincter deficiency is a debilitating condition for the patient and an ordeal for the urologist. Because of the complexity of reconstructive surgical techniques and the prohibitive cost of the prosthetic devices used, there is a need for a simple procedure. We herein report our experience in managing urinary incontinence secondary to sphincteric incompetence in nine consecutive patients using a modified bulbar urethral sling procedure over a period of 2 years. PATIENTS AND METHODS: In eight patients, the incontinence followed open prostatectomy or transurethral resection for benign prostatic hyperplasia, and one patient had incontinence following fulguration of posterior urethral valves. Our procedure uses bolsters that are suspended from the rectus fascia, and a hammock made of a folded Dacron patch is placed beneath the bulbospongiosus muscle to form a sling. RESULTS: All patients were continent postoperatively, with only mild stress leakage in the erect posture, during a mean follow-up of 12.2 months (range 6-22 months) and required one or two improvised pads per day to remain continent during the daytime. Persistent perineal infection necessitated removal of the sling in one patient. One patient required clean intermittent catheterization for a short period postoperatively. CONCLUSION: This modified bulbar urethral sling procedure is a simple yet effective method to treat sphincteric deficiency of any cause.

Molecular modeling, structure--activity relationships and functional antagonism studies of 4-hydroxy-1-methyl-4-(4-methylphenyl)-3-piperidyl 4-methylphenyl ketones as a novel class of dopamine transporter inhibitors.

We previously disclosed the discovery of 4-hydroxy-1-methyl-4-(4-methylphenyl)-3-piperidyl 4-methylphenyl ketone (3) as a novel class of dopamine transporter (DAT) inhibitors and showed that (+/-)-3 has a significant functional antagonism against cocaine in vitro. Our previous preliminary structure-activity relationship study led to identification of a more potent DAT inhibitor [(+/-)-4] but this compound failed to show any significant functional antagonism. To search for more potent analogues than 3 but still displaying significant functional antagonism, further SARs, molecular modeling studies and in vitro pharmacological evaluation of this novel class of DAT inhibitors were performed. Sixteen new analogues were synthesized in racemic form and evaluated as DAT inhibitors. It was found that seven new analogues are reasonably potent DAT inhibitors with K(i) values of 0.041--0.30 and 0.052--0.16 microM in [(3)H]mazindol binding and inhibition of DA reuptake. Chiral isomers of several potent DAT inhibitors were obtained through chiral HPLC separation and evaluated as inhibitors at all the three monoamine transporter sites. In general, the (-)-isomer is more active than the (+)-isomer in inhibition of DA reuptake and all the (-)-isomers are selective inhibitors at the DAT site. Evaluation of cocaine's effect on dopamine uptake in the presence and absence of (+)-3 and (-)-3 showed that (-)-3 is responsible for the functional antagonism obtained with the original lead (+/-)-3. Out of the new compounds synthesized, analogue (+/-)-20, which is 8- and 3-fold more potent than (+/-)-3 in binding and inhibition of DA reuptake, appeared to have improved functional antagonism as compared to (+/-)-3.

Pharmacophore-based discovery of 3,4-disubstituted pyrrolidines as a novel class of monoamine transporter inhibitors.

3,4-Disubstituted pyrrolidines were discovered as a novel class of monoamine transporter inhibitors through 3-D database pharmacophore searching using a new pharmacophore model. The most potent analogue 12 has Ki values of 0.084 microM in [3H]mazindol binding, 0.20, 0.23, and 0.031 microM in inhibition of dopamine (DA), serotonin (SER), and norepinephrine (NE) reuptake, respectively. Functional antagonism testing in vitro showed that 11 and 12 are weak cocaine antagonists.

Pharmacophore-based discovery, synthesis, and biological evaluation of 4-phenyl-1-arylalkyl piperidines as dopamine transporter inhibitors.

Pharmacophore-based discovery, synthesis, and structure activity relationship (SAR) of a series of 4-phenyl-1-arylalkyl piperidines are disclosed. These compounds have been evaluated for their ability to inhibit reuptake of dopamine (DA) into striatal nerve endings (synaptosomes). The lead compound 5 and the most potent analogue 43 were found to have significant functional antagonism.

Discovery of a novel dopamine transporter inhibitor, 4-hydroxy-1-methyl-4-(4-methylphenyl)-3-piperidyl 4-methylphenyl ketone, as a potential cocaine antagonist through 3D-database pharmacophore searching. Molecular modeling, structure-activity relationships, and behavioral pharmacological studies.

A novel, fairly potent dopamine transporter (DAT) inhibitor, 4-hydroxy-1-methyl-4-(4-methylphenyl)-3-piperidyl 4-methylphenyl ketone (3, K(i) values of 492 and 360 nM in binding affinity and inhibition of dopamine reuptake, respectively), with significant functional antagonism against cocaine and a different in vitro pharmacological profile from cocaine at the three transporter sites (dopamine, serotonin, and norepinephrine) was discovered through 3D-database pharmacophore searching. Through structure-activity relationships and molecular modeling studies, we found that hydrophobicity and conformational preference are two additional important parameters that determine affinity at the DAT site. Chemical modifications of the lead compound (3) led to a high affinity analogue (6, K(i) values of 11 and 55 nM in binding affinity and inhibition of dopamine reuptake, respectively). In behavioral pharmacological testing, 6 mimics partially the effect of cocaine in increasing locomotor activity in mice but lacks cocaine-like discriminative stimulus effect in rats. Taken together, these data suggest that 6 represents a promising lead for further evaluations as potential therapy for the treatment of cocaine abuse.

Intraoperative penile erection.

OBJECTIVE: Penile erection following epidural anesthesia is an infrequent occurrence of unclear etioogy. It is very troublesome to perform the procedure during penile erection and attempting it leads to various complications. Three such cases are reported herein. The literature on the pathophysiology and management of intraoperative penile erection is discussed. METHODS: Eighteen hundred patients who received epidural anesthesia for various transurethral procedures like cystoscopy, ureterorenoscopy, transurethral resection of prostate and bladder tumors form the clinical material. RESULTS: Out of 1800 cases, we have encountered penile erection only in three cases. Two cases were managed with local application of cold saline and cold sponging followed by terbutaline. The third case could be managed with local application of cold saline and cold sponging of scrotum and penis. Afterwards the procedure could be performed safely. CONCLUSION: The pathophysiology and management of intraoperative penile erection is poorly understood. With the onset of erection during an operative procedure, the anesthesiologist must quickly initiate the therapy, as duration of erection is the critical factor in the detumescence of the penis.

Fasting-induced suppression of hypothalamic-pituitary-gonadal axis in the adult rhesus monkey: evidence for involvement of excitatory amino acid neurotransmitters.

The present study was designed to examine whether acute food-restriction in non-human primates, suppresses hypothalamic-pituitary-testicular (HPT) axis via alterations in the excitatory amino acid (EAA) neurotransmitter-utilizing drive to the GnRH neuron. This was achieved indirectly by comparing the plasma testosterone (T) responses to administration of an excitatory amino acid analogue, N-methyl-D,L-aspartic acid (NMA), in acutely fasted and normal fed monkeys. A set of 4 chair-restrained adult male rhesus monkeys, was assigned to the following treatments: a) normal feeding, b) one-day fasting (omission of morning and afternoon meals), c) normal feeding+NMA (15 mg/kg BW) and d) one-day fasting+NMA (15 mg/kg BW). Starting 1 h after the provision or omission of the afternoon meal, frequent blood sampling was initiated at 15-min intervals for a period of 3-h. NMA was administered as an iv bolus 1 h after start of the sampling. Secretion of T was affected (P<0.005) by the treatments. A peak in T was evident during the first h of the sampling in fed but not fasted monkeys. Mean 3-h T concentrations were suppressed (P<0.001) by the fasting. Administration of NMA in fasting conditions resulted into an acute stimulation of T secretion in 2 of the 4 monkeys. However, mean 60-min post-NMA T concentrations were greater (P<0.05) than those prevailing during the same period in fasted animals not given NMA. In contrast, all 4 fed-monkeys showed significant T elevations in plasma immediately following the NMA challenge and mean T levels during the 60-min post-NMA period were higher (P<0.05) than those in fed animals not injected with NMA, at a comparable time. Testosterone area under the curve for the 2-h post-NMA period was greater (P<0.05) in fed- than in fasted-monkeys. These results indicate that although NMA can stimulate GnRH release both in fed and short-term fasting conditions, the response appears to be suppressed in the later situation suggesting that fasting-induced suppression of the HPT axis in the adult male rhesus monkey may involve a reduction in the sensitivity of GnRH neurons to the EAA neurotransmission.

Challenges in India and Bhutan.

PIP: While India is making overall progress in maternal and child health and reproductive health (MCH/RH), all states are not moving ahead. In fact, it is the states with the larger populations which are lagging behind. Primary education, women's status, and literacy remain problematic. UNFPA has worked in India for a long time, helping to realize the decline in total fertility rate from 6 to 3.5 over the past 20-30 years. India's population, however, is still growing at the annual rate of 1.8%. UNFPA's program in India for the period 1997-2001 will stress women's health as a matter of overall reproductive health, a new approach in India which has long relied upon sterilization. Attention must be given to meeting the needs of the poor in India as the country continues to grow in size and wealth. While Bhutan's estimated population is just over 1 million, the annual population growth rate of 3.1% threatens development over the long term. With a mountainous terrain and a low resource base, Bhutan cannot sustain a high population growth rate. Significant improvements have been made and women's status is good, the infant mortality rate has been reduced, and the health infrastructure is not bad. UNFPA's 5-year program beginning in 1998 will mainly address RH, especially adolescent RH.^ieng

Phosphatidic acid induces the release of beta-glucuronidase but not lactoferrin from electropermeabilized human neutrophils.

We studied the degranulation reaction of electropermeabilized human neutrophils induced by 1,2-didecanoyl-3-sn-phosphatidic acid (PA10). PA10 dose-dependently induced the release of beta-glucuronidase, an enzyme of azurophil granules, but did not induce the release of lactoferrin, a protein of specific granules. The enzyme release by PA10 absolutely required Ca2+, ATP, and Mg2+ and the concentrations for the half-maximal response were 2.5 microM, 60 microM, and 0.25 mM, respectively. Although Ca2+ alone at concentrations higher than 10 microM induced the release of both beta-glucuronidase and lactoferrin, the extents of the release were far less than that of the beta-glucuronidase release by PA10. Phorbol myristate acetate (PMA) and 1-oleoyl-2-acetyl-sn-glycerol induced the release of lactoferrin alone at concentrations of Ca2+ below 0.5 microM while they induced the release of both beta-glucuronidase and lactoferrin at higher Ca2+ concentrations, indicating that the degranulation induced by PA10 is not mediated by diacylglycerol which might be formed from PA. The degranulation reactions induced by PA10 and PMA were dose-dependently inhibited by staurosporine and calphostin C, protein kinase C inhibitors, although no direct activation of protein kinase C by PA10 was observed. The extent of the beta-glucuronidase release by PA10 was not enhanced by the addition of PMA. Propranolol, which inhibits protein kinase C as well as phosphatidic acid phosphohydrolase, strongly inhibited the degranulation reactions induced by PA10 and PMA. Ethanol, a metabolic modulator of phospholipase D, and cyclic AMP did not affect the degranulation reactions by PMA and PA10.(ABSTRACT TRUNCATED AT 250 WORDS)

Hematological and enzymatic results of aluminum intoxication in rats.

1. The study has been carried out on Wistar rats. The aim of the present study was to trace the effect of aluminum on enzyme activities and hematological parameters on erythrocytes. 2. Aluminum decreased activities of acetylcholinesterase, glutathione reductase, glucose-6-phosphate dehydrogenase, and lactate dehydrogenase in the erythrocytes of the animals tested. 3. In the peripheral blood, a significant decrease in the erythrocyte count, hemoglobin level and hematocrit index and increased percentage of reticulocytes and polychromatophilic erythrocytes were observed. 4. The increase in the neutrophilic granulocyte and lymphocyte count was significant. 5. An inhibitory effect of aluminum on the phagocytic activity of granulocytes was also observed.

Inhibition of delta aminolevulinic acid dehydratase activity by aluminum.

1. Studies were performed regarding the effects of aluminum chloride and aluminum nitrate in concentrations of 5 mg/kg of body weight on the delta aminolevulinic acid dehydratase activity, iron level and hematological parameters. Wistar rats were exposed to these pollutants for 10, 20, 40 and 80 days. 2. The results demonstrated that aluminum chloride was more toxic than aluminum nitrate and both treatments brought about significant changes in these parameters in Wistar rats bone marrow. 3. The toxic effects of aluminum chloride and aluminum nitrate are manifested by a significant decrease of delta aminolevulinic acid dehydratase activity in the bone marrow of rats. 4. The iron level in bone marrow with aluminum chloride and aluminum nitrate gradually dropped after 10, 20, 40 and 80 days of intoxication. 5. In the peripheral blood a significant decrease in the erythrocyte count, hemoglobin level, hematocrit value and an increase in mean corpuscular hemoglobin (MCH) were also found in experimental animals.

The world population situation.

PIP: Population experts appear to be reaching a consensus that there has been a perceptible decline over the last decade in the growth of the world's population. The decline is accounted for by the "new demographic transition" in the less developed countries (LDCs). The decline in fertility rates began in the 1950s in some LDCs and became more widespread during the 1970s. The process has not yet begun in many of the LDCs. During the 1960s it was observed that the declines in birth rates (to levels of 30 of less per 1000) were occurring mostly in small countries. Many of these countries were islands with levels of social and economic development above the developing country average. The key question is whether the recent downward trend in fertility in LDCs will continue, stabilize at the current level, or rise again. A primary concern about the future is that the poorer and less developed countries will end up with an increasing share of the world's population, with the share of the developed countries declining from 34% to 22% over the 1950-2000 period. Considerable differential exists in demographic growth patterns among various regions. The 12 largest LDCs (China, India, Indonesia, Brazil, Bangladesh, Pakistan, Nigeria, Mexico, Vietnam, Philippines, Thailand, Turkey) contain 55% of the current world population, and the fertility decline of these nations is expected to have the maximum impact. 7 of these countries have had fertility declines of 14-35%. The force of the "population momentum" must also be considered. Most developing country populations have a young age distribution with considerable potential for population growth even after the fertility level reaches a replacement level and the net reproduction rate equals 1.^ieng