COVID-19 health system response monitor: Japan

The COVID-19 Health System Response Monitor presents findings from a systematic approach to collect and synthesise up-to-date information on Singapore’s policy response to the COVID-19 outbreak. This publication is part of the APO’s COVID-19 HSRM series which presents detailed information on country-specific responses to COVID-19, to facilitate easy comparisons of health systems and public health, and policy responses to COVID-19. It also aims to strengthen evidence on the global response to the pandemic and allow for easy comparison of activities at national and sub-national levels. The series is updated to reflect changes in the health systems and policies to the COVID-19 response.

Role of serotonin 1A receptors in the median raphe nucleus on the behavioral consequences of forced swim stress.

Despite the intense research on the neurobiology of stress, the role of serotonin (5-HT)1A receptors still remains to be elucidated. In the hippocampus, post-synaptic 5-HT1A receptors activation induces anxiolytic effects in animals previously exposed to stressful situations. However, little is known about somatodendritic 5-HT1A receptors in the median raphe nucleus (MRN). Therefore, the aim of this study was to investigate the role of 5-HT1A receptors located in the MRN in rats exposed to forced swim stress. After recovering from surgery, rats were forced to swim for 15 min in a cylinder. Intra-MRN injections of saline, 8-OH-DPAT (3 nmol/0.2 µL) and/or WAY-100635 (0.3 nmol/0.2 µL) were performed immediately before or after pre-exposure or 24 h later (immediately before test). Non-stressed rats received the same treatment 24 h or 10 min before test. Our data showed that 8-OH-DPAT increased latency to display immobility while decreasing time spent immobile in almost all experimental conditions. These effects were not prevented by previous treatment with WAY-100635. No effects of different treatments were described in non-stressed animals. Taken together, our data suggest that in addition to activation of 5-HT1A, 5-HT7 receptors may also be involved in the behavioural consequences of exposure to swim stress.

Effects of topical instillation of minocycline hydrochloride on cyst size and renal function in polycystic kidney disease.

To reduce renal cyst size in autosomal dominant polycystic kidney disease (ADPKD), minocycline hydrochloride solution was instilled into the enlarged cysts in three ADPKD patients. In one patient with reduced renal function, such sclerotherapy apparently diminished cyst size, but without apparent improving effect on renal function at 7 months of follow-up. The second patient, who needed the replacement therapy on admission, had been free from hemodialysis over 4 months after the therapy. Persistent flank pain disappeared in both patients. In the third patient with normal renal function, sclerotherapy was done to get a better control of hypertension. Initially blood pressure decreased, but it returned up to the pre-therapy level irrespective of definite reduction of the enlarged cysts at 8 months of follow-up. The therapy with minocycline hydrochloride did not appear harmful, and may be helpful in the management of ADPKD.

Increased internal calcium mobilization in platelets of patients with chronic renal failure.

Platelet free calcium concentrations ([Ca2+]i) were measured with Fura-2 to elucidate the intracellular calcium kinetics in patients with renal disease. There were no significant differences of the resting [Ca2+]i among the control subjects (C) (n = 12), patients with chronic glomerulonephritis (CGN) (n = 8), and patients with chronic renal failure (CRF) (n = 12). In all groups, platelets [Ca2+]i were significantly increased by agonists (thrombin, adenosine diphosphate) compared with their respective basal level. Thrombin-induced [Ca2+]i rise was significantly higher in CRF (840 +/- 265 nM) than in C (600 +/- 163) and CGN (562 +/- 137). Also adenosine diphosphate elicited similar responses. In the presence of calcium chelator in the incubation buffer, the elevation of [Ca2+]i after thrombin stimulation was statistically higher in CRF (469 +/- 85 nM) than in C (275 +/- 60) and CGN (301 +/- 41). These findings suggest that platelets of CRF were capable of increasing [Ca2+]i in response to agonists, through further mobilization of calcium from the intracellular pool rather than the elevation of transmembrane calcium influx.

Reduced glomerular hypertrophy by somatostatin analog, SMS 201-995, in the subtotal nephrectomized rats fed high-protein meals.

The chronic effects of SMS 201-995 (SMS), a long-acting somatostatin analog, on the progression of renal failure in 3/4 subtotal nephrectomized rats (NPX) fed high protein meals (40% protein) were investigated. Rats were divided into four groups, [i.e., normal control (C) (n = 6), NPX control (NPX-C) (7), NPX treated with SMS 1.0 micrograms/day (SMS-1.0) (7) and SMS-10.0 (7)]. SMS was continuously administered s.c. via an osmotically driven pump for 8 weeks. SMS had no significant changes in either body weight or hematocrit levels for NPX groups. Systolic blood pressure in NPX rats showed similar elevations, but SMS had no distinct effect on it for them. Significant changes in urine volume, creatinine clearance, and urinary protein excretion were not obtained among the NPX rats. No significant changes of glomerular sclerosis index was found among the NPX rats. Mean planar area of glomeruli in NPX rats was significantly larger than in normal control rats. NPX treated with both 1.0 and 10.0 micrograms/day SMS had statistically smaller values compared with NPX control rats. It was concluded that the chronic administration of SMS reduced glomerular hypertrophy without altering renal functions in this experimental model.

Effect of glucagon infusion on renal hemodynamics in normal subjects and patients with chronic glomerulonephritis.

The effect of glucagon infusion (15-20 ng/kg/min, for one hour) on renal hemodynamics was examined in normal subjects and in patients with chronic glomerulonephritis (CGN). In normal subjects, the glomerular filtration rate (GFR) was significantly increased by glucagon with a concomitant rise in effective renal plasma flow (ERPF) and filtration fraction (FF) (GFR/ERPF). In renal patients with a baseline GFR of above 90 ml/min/l/73 m2, GFR was significantly increased in response to glucagon, without a significant rise in ERPF. The patients whose baseline GFR ranged from 40-90 ml/min had no significant increase in GFR, while ERPF rose significantly. These results suggest that the renal hemodynamic response to glucagon infusion were modified by the level of baseline GFR in patients with chronic glomerulonephritis.

Effects of chronic administration of somatostatin analogue SMS 201-995 on the progression of chronic renal failure in subtotal nephrectomized rats.

The recent study has demonstrated the presence of somatostatin (SRIF) secretory cells in the rat glomerulus. Because of the polyvalent actions of this peptide, SRIF may play some roles in the evolution of chronic renal failure. The present study evaluated the effects of a long acting SRIF analogue, SMS 201-995 on the progression of renal failure in 3/4 nephrectomized (NPX) rats. Animals were divided into four groups; (1) normal control (C) (n = 9), (2) NPX-C (n = 10), (3) NPX treated with SMS 201-995 (0.5 micrograms/day) (NPX-0.5) (n = 9) and (4) NPX with SMS 201-995 (5.0 micrograms/day) (NPX-5.0) (n = 9). This drug was subcutaneously given daily for 6 weeks. Periodic observations were done at 0, 3 and 6 weeks. Both hematocrit and systolic blood pressure showed significant fall and rise, respectively, in NPX rats compared with C at 3 and 6 weeks. Also both serum creatinine and blood urea nitrogen in these groups elevated significantly at 3 and 6 weeks compared with C. Not significant changes were observed in the 24-h urine volume among the NPX rats. At 6 weeks, the urinary protein excretion in NPX-5.0 was significantly less than those in NPX-C and NPX-0.5 rats. Urinary sodium excretion in NPX-5.0 was significantly lower than that in NPX-C. Histologic examination of the kidney showed less proliferation of mesangial cells in NPX-5.0 than NPX-C. These results suggest that SMS 201-995 may limit the rate of progression of chronic renal failure in this experimental model.