Low-Rank Combinatorial Optimization and Statistical Learning by Spatial Photonic Ising Machine.

The spatial photonic Ising machine (SPIM) [13D. Pierangeli et al., Large-Scale Photonic Ising Machine by Spatial Light Modulation, Phys. Rev. Lett. 122, 213902 (2019).PRLTAO0031-900710.1103/PhysRevLett.122.213902] is a promising optical architecture utilizing spatial light modulation for solving large-scale combinatorial optimization problems efficiently. The primitive version of the SPIM, however, can accommodate Ising problems with only rank-one interaction matrices. In this Letter, we propose a new computing model for the SPIM that can accommodate any Ising problem without changing its optical implementation. The proposed model is particularly efficient for Ising problems with low-rank interaction matrices, such as knapsack problems. Moreover, it acquires the learning ability of Boltzmann machines. We demonstrate that learning, classification, and sampling of the MNIST handwritten digit images are achieved efficiently using the model with low-rank interactions. Thus, the proposed model exhibits higher practical applicability to various problems of combinatorial optimization and statistical learning, without losing the scalability inherent in the SPIM architecture.

Spatial-photonic Ising machine by space-division multiplexing with physically tunable coefficients of a multi-component model.

This paper proposes a space-division multiplexed spatial-photonic Ising machine (SDM-SPIM) that physically calculates the weighted sum of the Ising Hamiltonians for individual components in a multi-component model. Space-division multiplexing enables tuning a set of weight coefficients as an optical parameter and obtaining the desired Ising Hamiltonian at a time. We solved knapsack problems to verify the system's validity, demonstrating that optical parameters impact the search property. We also investigated a new dynamic coefficient search algorithm to enhance search performance. The SDM-SPIM would physically calculate the Hamiltonian and a part of the optimization with an electronics process.

Infinite ergodicity that preserves the Lebesgue measure.

In this study, we prove that a countably infinite number of one-parameterized one-dimensional dynamical systems preserve the Lebesgue measure and are ergodic for the measure. The systems we consider connect the parameter region in which dynamical systems are exact and the one in which almost all orbits diverge to infinity and correspond to the critical points of the parameter in which weak chaos tends to occur (the Lyapunov exponent converging to zero). These results are a generalization of the work by Adler and Weiss. Using numerical simulation, we show that the distributions of the normalized Lyapunov exponent for these systems obey the Mittag-Leffler distribution of order 1/2.

Targeted RNA sequencing with touch imprint cytology samples for non-small cell lung cancer patients.

BACKGROUND: RNA-based sequencing is considered ideal for detecting pathogenic fusion-genes compared to DNA-based assays and provides valuable information about the relative expression of driver genes. However, RNA from formalin-fixed paraffin-embedded tissue has issues with both quantity and quality, making RNA-based sequencing difficult in clinical practice. Analyzing stamp-derived RNA with next-generation sequencing (NGS) can address the above-mentioned obstacles. In this study, we validated the analytical specifications and clinical performance of our custom panel for RNA-based assays on the Ion Torrent platform. METHODS: To evaluate our custom RNA lung panel, we first examined the gene sequences of RNA derived from 35 NSCLC tissues with diverse backgrounds by conventional methods and NGS. Next, we moved to the clinical phase, where clinical samples (all stamp-derived RNA) were used to examine variants. In the clinical phase we conducted an NGS analysis while simultaneously applying conventional approaches to assess the feasibility and validity of the panel in clinical practice. RESULTS: In the prerun phase, all of the variants confirmed with conventional methods were detected by NGS. In the clinical phase, a total of 80 patients were enrolled and 80 tumor specimens were sequenced from February 2018 to December 2018. There were 66 cases in which the RNA concentration was too low to be measured, but sequencing was successful in the vast majority of cases. The concordance between NGS and conventional methods was 95.0%. CONCLUSIONS: RNA extraction using stamp specimens and panel sequencing by NGS were considered applicable in clinical settings. KEY POINTS: Significant findings of the study Next-generation sequencing using RNA from stamp specimens was able to detect driver gene changes in non-small cell lung cancer including fusion genes with the same accuracy as conventional methods. What this study adds Using RNA from stamp specimens obtained from biopsy increases the number of candidate cases for RNA sequencing in clinical settings.

Rationale design of quorum-quenching peptides that target the VirSR system of Clostridium perfringens.

In Clostridium perfringens, a 5-membered thiolactone peptide acts as an autoinducing peptide (AIPCp) to activate the VirSR two-component signal transduction system, which in turn controls the expression of genes encoding multiple toxins, including α, θ and κ. To develop anti-pathogenic agents against virulent C. perfringens, quorum-quenching peptides were rationally designed based on the structure-activity relationship (SAR) data on AIPCp. Alanine scanning study of AIPCp suggested that Trp(3) and Phe(4) are involved in receptor binding and activation, respectively. On the basis of the SAR, we designed two quorum-quenching peptides with different modes of action: Z-AIPCp-L2A/T5A (partial agonist) and Z-AIPCp-F4A/T5S (partial antagonist). Both peptides significantly attenuated transcription of θ toxin gene (pfoA) in a virulent strain of C. perfringens with IC50 = 0.32 and 0.72 µM, respectively.

Cyclodepsipeptides produced by actinomycetes inhibit cyclic-peptide-mediated quorum sensing in Gram-positive bacteria.

Cyclic peptides are commonly used as quorum-sensing autoinducers in Gram-positive Firmicutes bacteria. Well-studied examples of such molecules are thiolactone and lactone, used to regulate the expression of a series of virulence genes in the agr system of Staphylococcus aureus and the fsr system of Enterococcus faecalis, respectively. Three cyclodepsipeptides WS9326A, WS9326B and cochinmicin II/III were identified as a result of screening actinomycetes culture extracts for activity against the agr/fsr system. These molecules are already known as receptor antagonists, the first two for tachykinin and the last one for endothelin. WS9326A also inhibited the transcription of pfoA regulated by the VirSR two-component system in Clostridium perfringens. Receptor-binding assays using a fluorescence-labeled autoinducer (FITC-GBAP) showed that WS9326A and WS9326B act as receptor antagonists in this system. In addition, an ex vivo assay showed that WS9326B substantially attenuated the toxicity of S. aureus for human corneal epithelial cells. These results suggest that these three natural cyclodepsipeptides have therapeutic potential for targeting the cyclic peptide-mediated quorum sensing of Gram-positive pathogens.

Phase II study of adjuvant vinorelbine and cisplatin in Japanese patients with completely resected stage II and III non-small cell lung cancer.

PURPOSE: Adjuvant vinorelbine and cisplatin chemotherapy is recognized as a standard regimen for patients with completely resected stage II and III non-small cell lung cancer (NSCLC). However, efficacy of adjuvant chemotherapy in Japanese phase III trials with cisplatin-containing regimen has been controversial, and data are limited on the long-term outcome of adjuvant vinorelbine and cisplatin chemotherapy for NSCLC patients. METHODS: This was a single-arm phase II study in patients with completely resected pathological stage II or III NSCLC, who had not received prior chemotherapy or radiotherapy. Patients received 4 cycles of vinorelbine [25 mg/m(2) of body surface area (BSA)] and cisplatin (40 mg/m(2) of BSA) on days 1 and 8, every 4 weeks. Primary end point was the 3-year relapse-free survival; secondary end points were overall survival and safety. RESULTS: Between December 2006 and January 2011, 60 patients (40 men and 20 women, median age 64 years) were enrolled; all patients were evaluable for survival and safety. Three-year relapse-free survival rate was 55.0 % (95 % confidence interval 42.4-67.6 %). Three- and five-year overall survival rates were 83.3 and 77.8 %, respectively. There were no chemotherapy-related deaths, and adverse effects were acceptable. CONCLUSIONS: Adjuvant vinorelbine and cisplatin chemotherapy was safe and showed a valid relapse-free survival rate. This regimen could be used as a standard regimen and deserves to be a control arm of trials on adjuvant chemotherapy in the Japanese NSCLC patient population.

C-reactive protein and risk of first-ever ischemic and hemorrhagic stroke in a general Japanese population: the Hisayama Study.

BACKGROUND AND PURPOSE: The role of high-sensitivity C-reactive protein (hsCRP) in the development of stroke is not clearly understood. We investigated the relationship between serum hsCRP levels and stroke occurrence in a general Japanese population. METHODS: We followed 2692 subjects > or =40 years of age for 12 years. The relative risks and 95% CIs for ischemic and hemorrhagic stroke occurrence were calculated according to the hsCRP quintiles. RESULTS: During the follow-up, 129 first-ever ischemic and 59 hemorrhagic strokes occurred. In men, the age-adjusted incidence of ischemic stroke significantly increased with elevated serum hsCRP levels; the difference between the first and fifth quintiles was statistically significant (1.4 versus 6.6 per 1000 person-years; P=0.02). This association remained significant even after adjustment for other confounding factors, such as age, systolic blood pressure, ECG abnormalities, diabetes, body mass index, total cholesterol, high-density lipoprotein cholesterol, smoking habits, alcohol intake, and regular exercise (adjusted relative risks, 3.11; 95% CI, 1.04 to 9.32; P=0.04). However, such associations were not observed for ischemic stroke in women or in hemorrhagic stroke in either sex. Among male subjects who were both in the fifth hsCRP level and had hypertension, diabetes, obesity, hypercholesterolemia, or a smoking habit, the risk of ischemic stroke was extremely increased, even after adjustment for other risk factors. CONCLUSIONS: Our findings suggest that elevated serum hsCRP levels are an independent risk factor for future ischemic stroke in Japanese men and that the coexistence of a high hsCRP level with another risk factor extremely increases the risk of ischemic stroke.

Role of protein kinase C in Ca channel blocker-induced renal arteriolar dilation in spontaneously hypertensive rats--studies in the isolated perfused hydronephrotic kidney.

The present study examined the role of L-/T-type Ca channels and the interaction between these channels and protein kinase C (PKC) in hypertension. The isolated perfused hydronephrotic rat kidney model was used to visualize directly the renal microvascular effects of L-/T-type Ca channel blockers (nifedipine and mibefradil, respectively). Nifedipine reversed the angiotensin II-induced constriction of afferent, but not efferent, arterioles in kidneys from Wistar-Kyoto rats (WKY), and similar magnitude in dilation was observed in spontaneously hypertensive rats (SHR). Although mibefradil elicited dilation of both arterioles, the afferent arteriolar dilation was less in SHR than in WKY (57+/-5% vs. 80+/-4% reversal at 1 micrommol/L). The pretreatment with staurosporine did not alter the angiotensin II-induced afferent arteriolar constriction in WKY, but attenuated this response in SHR. Furthermore, staurosporine enhanced the nifedipine-induced afferent arteriolar dilation (62+/-3% vs. 50+/-3% reversal at 10 nmol/L), and restored the attenuated afferent arteriolar response to mibefradil in SHR. The pretreatment with thapsigargin (a blocker of IP3-mediated intracellular calcium release) prevented the angiotensin II-induced afferent arteriolar constriction in WKY, but caused a significant constriction of afferent arterioles in SHR and efferent arterioles in WKY and SHR; in this setting, mibefradil did not alter efferent arteriolar tone. In conclusion, although both L-type (nifedipine) and T-type Ca channel blockers (mibefradil) exerted potent vasodilation of rat renal microvessels, these actions were modified by PKC, which determined the afferent arteriolar sensitivity to these blockers in SHR. Furthermore, the enhancement in nifedipine-induced afferent arteriolar dilation by staurosporine in SHR suggests that L-type Ca channel activity is augmented in hypertensive animals.

Role of asymmetrical dimethylarginine in renal microvascular endothelial dysfunction in chronic renal failure with hypertension.

We examined whether endothelial function of the renal microcirculation was impaired in a model of chronic renal failure (CRF), and further assessed the role of asymmetrical dimethylarginine (ADMA) and its degrading enzyme, dimethylarginine dimethylaminohydrolase (DDAH), in mediating the deranged nitric oxide (NO) synthesis in CRF. CRF was established in male mongrel dogs by subtotal nephrectomy, and the animals were used in experiments after a period of 4 weeks. The endothelial function of the renal afferent and efferent arterioles was evaluated according to the response to acetylcholine, using an intravital needle-lens charge-coupled device camera. Intrarenal arterial infusion of acetylcholine (0.01 microg/kg/min) elicited 22+/-2% and 20+/-2% dilation of the afferent and efferent arterioles in normal dogs. In dogs with CRF, this vasodilation was attenuated (afferent, 12+/-2%; efferent, 11+/-1%), and the attenuation paralleled the diminished increments in urinary nitrite+nitrate excretion. In the animals with CRF, plasma concentrations of homocysteine (12.2+/-0.7 vs. 6.8+/-0.4 micromol/l) and ADMA were elevated (2.60+/-0.13 vs. 1.50+/-0.08 micromol/l). The inhibition of S-adenosylmethionine-dependent protein arginine N-methyltransferase by adenosine dialdehyde decreased plasma ADMA levels, and improved the acetylcholine-induced changes in urinary nitrite+nitrate excretion and arteriolar vasodilation. Acute methionine loading impaired the acetylcholine-induced renal arteriolar vasodilation in CRF, but not normal dogs, and the impairment in CRF dogs coincided with the changes in plasma ADMA levels. Real-time polymerase chain reaction revealed downregulation of the mRNA expression of DDAH-II in the dogs with CRF. Collectively, these results provide direct in vivo evidence of endothelial dysfunction in canine CRF kidneys. The endothelial dysfunction was attributed to the inhibition of the NO production by elevated ADMA, which involved the downregulation of DDAH-II. The deranged NO metabolic pathway including ADMA and DDAH is a novel mechanism for the aggravation of renal function.

Secular trends in the incidence, mortality, and survival rate of gastric cancer in a general Japanese population: the Hisayama study.

To examine secular trends in the incidence and mortality of gastric cancer in a Japanese community, Hisayama, we established three study-cohorts of Hisayama residents aged > or =40 years in 1961 (1637 subjects), 1974 (2054), and 1988 (2602). Each cohort was followed up for ten years. The age-standardized mortality from gastric cancer significantly decreased from 2.4 per 1000 person-years in the first cohort to 0.8 in the third cohort for men, and from 1.0 to 0.2, respectively, for women (p < 0.01 for trend in both sexes). The five-year survival rate after gastric cancer significantly improved from the first (32.6%) to the third cohort (73.0%, p < 0.01) for men and from 43.2% to 72.3% (p < 0.05), respectively, for women. The age-standardized incidence of cancer in men was not different among the cohorts (4.3 per 1000 person-years in the first, 5.0 in the second, and 4.9 in the third cohort), while it decreased significantly in women (2.0, 1.8, and 1.2, respectively, p < 0.01 for trend). In conclusion, our findings suggest that in a Japanese population, the mortality from gastric cancer declined during the past 40 years, due mainly to the improvement of survival in both sexes and a decrease in the incidence for women.

Chronic kidney disease and cardiovascular disease in a general Japanese population: the Hisayama Study.

BACKGROUND: Chronic kidney disease has been shown to be an independent risk factor for cardiovascular disease in high-risk populations. However, this relationship is inconclusive in community-based populations. METHODS: To clarify this issue, we followed 2634 community-dwelling individuals without cardiovascular disease, aged 40 years or older, for 12 years and examined the relationship between chronic kidney disease and the incidence of cardiovascular disease. RESULTS: During the follow-up period, 99 subjects (56 men and 43 women) experienced coronary heart disease, 137 subjects (60 men and 77 women) ischemic stroke, and 60 subjects (26 men and 34 women) hemorrhagic stroke. In men, the age-adjusted incidence of coronary heart disease was significantly higher in subjects with chronic kidney disease than in those without it (6.2 vs. 2.9 per 1000 person-years) (P < 0.05), but such a relationship was not observed with ischemic stroke. In contrast, in women, the age-adjusted incidence of ischemic stroke was significantly higher in subjects with chronic kidney disease than in those without it (3.4 vs. 2.5) (P < 0.05), while that of coronary heart disease was not. Chronic kidney disease was not found to be associated with the incidence of hemorrhagic stroke. In multivariate analysis, even after adjustments for traditional and nontraditional cardiovascular disease risk factors, chronic kidney disease was found to be an independent risk factor for the occurrence of coronary heart disease in men [hazard ratio (HR), 2.26; 95% CI, 1.06-4.79], and for the occurrence of ischemic stroke in women (HR, 1.91; 95% CI, 1.15-3.15). CONCLUSION: Our findings suggest that chronic kidney disease is an independent risk factor for the occurrence of cardiovascular disease in the general Japanese population.

Hyperhomocysteinemia and the development of chronic kidney disease in a general population: the Hisayama study.

BACKGROUND: Hyperhomocysteinemia has been linked with various atherosclerotic diseases, but has not been evaluated sufficiently as a risk factor for the development of chronic kidney disease (CKD) in the general population. METHODS: To clarify this issue, we followed up 1,477 community-dwelling individuals without CKD, aged 40 years or older, for 5 years and examined the effects of baseline serum total homocysteine (tHcy) levels on the development of CKD. RESULTS: During follow-up, 88 subjects experienced CKD. Baseline tHcy levels were greater in men than women (1.35 versus 1.04 mg/L [10.0 versus 7.7 micromol/L]; P < 0.01). Age-adjusted 5-year incidences were 2.2% in the low tertile, 5.4% in the middle tertile, and 8.6% in the high tertile of tHcy levels for men and 3.3%, 6.0%, and 6.9% for women, respectively. The difference between the low and high tertiles was statistically significant for both sexes ( P < 0.05). In multivariate analysis, these relationships remained substantially unchanged, even after adjustment for other confounding factors, such as systolic blood pressure, antihypertensive medication, hemoglobin A 1c level, total cholesterol level, high-density lipoprotein cholesterol level, habitual smoker status, regular alcohol intake, proteinuria, and baseline kidney function (odds ratio [OR] in the high tertile of tHcy levels, 2.09; 95% confidence interval [CI], 0.66 to 6.61 for men; OR, 2.86; 95% CI, 1.10 to 7.43 for women). Furthermore, baseline tHcy level showed a significantly inverse association with rate of change in kidney function during the 5 years after being adjusted for confounding factors, including baseline kidney function. CONCLUSION: Our findings suggest that elevated serum tHcy levels are a significant risk factor for the development of CKD in the general population.

Trends in the incidence, mortality, and survival rate of cardiovascular disease in a Japanese community: the Hisayama study.

BACKGROUND AND PURPOSE: The slowdown of a steeply declining trend in cardiovascular mortality has been reported in Japan, but precise reasons for this trend are uncertain. METHODS: We established 3 study cohorts of Hisayama residents aged > or =40 years without a history of stroke or myocardial infarction in 1961 (1618 subjects, first cohort), 1974 (2038 subjects, second cohort), and 1988 (2637 subjects, third cohort). We followed up with each cohort for 12 years, comparing the incidence, mortality, and survival rate of cardiovascular disease. RESULTS: The age-adjusted incidence of cerebral infarction significantly declined by 37% for men and by 32% for women from the first to the second cohort. It continued to decline by 29% for men, but the decline decelerated for women in the third cohort. The incidence of cerebral hemorrhage steeply declined by 61% from the first to the second cohort in men only, while it was sustained for both sexes in the third cohort. Stroke mortality continuously declined as a result of these incidence changes and significant improvement of survival. In contrast, the incidence and mortality rate of coronary heart disease were unchanged except for the increasing incidence in the elderly. The prevalence of severe hypertension and current smoking significantly decreased, while that of glucose intolerance, hypercholesterolemia, and obesity greatly increased among the cohorts. CONCLUSIONS: Our data suggest that the decline in stroke incidence is slowing down and that the incidence of coronary heart disease has been increasing in the elderly in recent years. Insufficient control of hypertension and the increase in metabolic disorders may contribute to these trends.

Ten-year prognosis of stroke and risk factors for death in a Japanese community: the Hisayama study.

BACKGROUND AND PURPOSE: There have been very few population-based cohort studies of long-term prognosis and risk factors for death after stroke. We examined the 10-year prognosis, causes, and risk factors of death after stroke in a Japanese cohort. METHODS: During a 26-year follow-up of a cohort of 1621 subjects > or =40 years of age, 333 subjects developed first-ever stroke and were prospectively followed up for 10 years after onset. During these 10-year follow-up periods, 268 of the 333 stroke patients died. Of those, 239 (89.2%) underwent autopsy. RESULTS: The risk of death was greatest in the first year after first-stroke onset in both sexes (men, 40.3%; women, 43.7%). Thereafter, the survival curves decreased gradually, and risk of death reached 80.7% for men and 80.2% for women by the end of the 10-year follow-up. The 30-day case fatality rate was substantially greater in patients with cerebral hemorrhage (63.3%) or subarachnoid hemorrhage (58.6%) than in patients with cerebral infarction (9.0%). The risk of dying after the first stroke was twice the risk for stroke-free subjects. The most common cause of death was the index stroke in the first year. Thereafter, the impact of the first stroke gradually decreased, while that of recurrent stroke increased. Multivariate analysis revealed that age, lower body mass index, and hemorrhagic stroke were significant risk factors for death after stroke. CONCLUSIONS: Our findings suggest that the risk of death after first-ever stroke is high, in part because of the larger proportion of hemorrhagic stroke in Japanese relative to stroke victims in Western countries.

Vessel- and vasoconstrictor-dependent role of rho/rho-kinase in renal microvascular tone.

We examined the role of Rho/Rho-kinase in renal afferent and efferent arteriolar tone induced by angiotensin (Ang) II, KCl and elevated renal arterial pressure (from 80 to 180 mm Hg), using isolated perfused rat hydronephrotic kidney. In the condition with no vasoconstrictor stimuli, Y-27632, a Rho-kinase inhibitor, dilated only afferent (from 11.6 +/- 0.4 to 14.1 +/- 0.5 microm) but not efferent arterioles (from 11.6 +/- 0.2 to 12.6 +/- 0.7 microm) at 10(-5) mol/l. During renal vasoconstriction by Ang II, Y-27632 restored the afferent arteriolar constriction (141 +/- 10% reversal at 10(-5) mol/l), whereas the ability of Y-27632 to inhibit the Ang II-induced efferent arteriolar constriction was diminished (73 +/- 7% reversal). A similar action was observed with fasudil, another Rho-kinase inhibitor. Furthermore, Y-27632 impaired myogenic afferent arteriolar constriction, with 117 +/- 17% inhibition at 10(-5) mol/l. The inhibition by Y-27632 of the myogenic vasoconstriction was almost the same as that of the Ang II-induced tone of this vessel type. However, Y-27632 had a modest effect on KCl-induced vasoconstriction of afferent arterioles. In conclusion, the present study demonstrates a predominant role of Rho/Rho-kinase in mediating the basal and Ang II-induced tone of afferent, but not efferent, arterioles. Furthermore, the role of Rho/Rho-kinase in afferent arteriolar constriction differs, with a substantial contribution to Ang II-induced and myogenic constriction but a minimal role in depolarization-induced constriction. Since Ang II-induced, KCl-induced and myogenic constriction of afferent arterioles require calcium entry through voltage-dependent calcium channels, the interaction between Rho/Rho-kinase and the calcium entry pathway may determine the afferent arteriolar tone induced by these stimuli.

[Hypertension in patients with diabetes mellitus].

It is well known that diabetes often induces macrovascular and microvascular complications, and hypertension is also considered to be an important risk factor for macrovascular events. Recent epidemiological studies have proved the possibility that hypertension among patients with diabetes greatly increases the risks of these complications. However, the impact of hypertension on stroke and microvascular complications is considered to be greater than that on coronary heart disease. Co-existent metabolic risk factors such as hyperlipidemia rather than hypertension may affect more coronary heart disease. Antihypertensive treatment among diabetic patients is expected to reduce various complications, but management of metabolic risk factors is also needed to prevent coronary heart disease.

Age- and sex-specific prevalence of diabetes and impaired glucose regulation in 11 Asian cohorts.

OBJECTIVE: To report the age- and sex-specific prevalence of diabetes and impaired glucose regulation (IGR) according to revised World Health Organization criteria for diabetes in Asian populations. RESEARCH DESIGN AND METHODS: We performed 11 studies of 4 countries, comprising 24,335 subjects (10,851 men and 13,484 women) aged 30-89 years who attended the 2-h oral glucose tolerance test and met the inclusion criteria for data analysis. RESULTS: The prevalence of diabetes increased with age and reached the peak at 70-89 years of age in Chinese and Japanese subjects but peaked at 60-69 years of age followed by a decline at the 70 years of age in Indian subjects. At 30-79 years of age, the 10-year age-specific prevalence of diabetes was higher in Indian than in Chinese and Japanese subjects. Indian subjects also had a higher prevalence of IGR in the younger age-groups (30-49 years) compared with that for Chinese and Japanese subjects. Impaired glucose tolerance was more prevalent than impaired fasting glycemia in all Asian populations studied for all age-groups. CONCLUSIONS: Indians had the highest prevalence of diabetes among Asian countries. The age at which the peak prevalence of diabetes was reached was approximately 10 years younger in Indian compared with Chinese and Japanese subjects. Diabetes and IGR will be underestimated in Asians based on the fasting glucose testing alone.

Role of nitric oxide and prostaglandin E2 in acute renal hypoperfusion.

Although acute renal ischaemia alters the production of various paracrines, there has been little investigation examining the role of intrarenal vasoactive substances. In the present study, we investigated the role of intrarenal nitric oxide and prostaglandins in modulating the acute renal hypoperfusion-induced alterations in renal function. After a 90% clipping of the left renal artery for 60 min, the clip was released, and the renal haemodynamics and sodium excretion were evaluated in both clipped and non-clipped kidneys of anaesthetized dogs. Furthermore, the changes in renal contents of nitrate/nitrite (NOx) and prostaglandin E2 (PGE2) were assessed by using the renal microdialysis technique. The release of the clipping elicited a gradual recovery of renal plasma flow and glomerular filtration rate, and a sustained increase in fractional sodium excretion (FENa) in the clipped kidney. Renal interstitial NOx was reduced in both the cortex (from 8.2 +/- 1.1 to 2.5 +/- 0.3 micromol/L, P < 0.01) and medulla (from 10.1 +/- 0.9 to 3.1 +/- 0.2 micromol/L, P < 0.01), but the levels gradually elevated after declamping. The treatment with nitro-l-arginine methylester only modestly impaired the recovery of renal plasma flow (RPF; at hour 4) and glomerular filtration rate (GFR; at hours 3 and 4 after declamping), without affecting FENa. Conversely, the renal PGE2 levels increased prominently upon the onset of ischaemia (medulla, from 149 +/- 19 to 378 +/- 39 pg/mL, P < 0.01; cortex, from 107 +/- 13 to 302 +/- 34 pg/mL, P < 0.01). Furthermore, the pretreatment with a non-specific cyclo-oxygenase (COX) inhibitor, sulpyrine, and a COX-2-specific inhibitor, NS398, prominently inhibited the increases in FENa induced by the acute renal arterial clipping in a similar manner. In conclusion, in acute renal hypoperfusion, nitric oxide (NO) plays a permissive role in the recovery of the renal haemodynamics. In contrast, sustained increases in renal PGE2 in both clipped and non-clipped kidneys indicate that the COX-2-mediated PGE2 contributes importantly to the failure of the sodium reabsorption in response to acute renal hypoperfusion.