Clinical and Experimental Pharmacology and Physiology

1. Plasma levels of ANP were measured in normal subjects and in three conditions associated with disturbed volume homeostasis.

2. Levels of ANP were appropriately raised in seven patients with primary aldosteronism, and fell to normal following removal of an aldosterone‐producing adenoma in six and dexamethasone treatment in one patient with glucocorticoid‐suppressible hyperaldosteronism.

3. The level of ANP in one patient with Gordon's syndrome (a condition associated with plasma volume expansion) was lower than in the patients with primary aldosteronism, both before and after saline infusion. This is consistent with reduced ANP responsiveness in this condition.

4. Levels of ANP were inappropriately elevated in three patients with Bartter's syndrome (a condition with plasma volume contraction) and rose further during saline infusion. This is consistent with primary hypersecretion of ANP.

1. Renal handling of electrolytes, including calcium (Ca), in response to physiological saline infusion (20 mL/kg, i.v., for 2 h) as well as basal circulating levels of Ca‐regulating hormones were compared in 27 hypertensive elderly females (mean age 80±9 years), in 44 normotensive elderly females (79±9 years) and in 19 young normotensive females (23±4 years).

2. The hypertensive elderly females showed excessive increase in urine volume and urinary excretions of sodium (Na), Ca and inorganic phosphate (P) in response to saline infusion, associated with slight but significant decrease in circulating levels of Na and ionized Ca compared with those in the other groups. These hypertensive elderly patients also showed characteristic features both in circulating blood pressure and Ca regulating factors; they showed significantly low levels of plasma renin activity and aldosterone concentration, significantly high plasma levels of atrial natriuretic peptide and noradrenalin, compared with those in young controls and normotensive elderly females.

3. Moreover they showed significant increase in basal serum levels of parathyroid hormone and 1,25‐dihydroxyvitamin D, and significant decrease in basal serum levels of calcitonin, 25‐hydroxy‐vitamin D and 24,25‐dihydroxyvitamin D, compared with those in the other groups.

4. These results suggest that the exaggerated natriuresis associated with excessive loss of Ca and P in urine may participate in the abnormality of Ca metabolism in low‐renin hypertensive elderly patients.

1. Curcumin là thành phần hoạt tính của gia vị nghệ và đã được tiêu dùng cho mục đích y học từ hàng nghìn năm nay. Khoa học hiện đại đã chỉ ra rằng curcumin điều chỉnh nhiều phân tử tín hiệu khác nhau, bao gồm các phân tử gây viêm, yếu tố phiên mã, enzym, protein kinase, protein reductase, protein mang, protein giúp tế bào sống sót, protein kháng thuốc, phân tử bám dính, yếu tố tăng trưởng, thụ thể, protein điều hòa chu kỳ tế bào, chemokine, DNA, RNA và ion kim loại.

2. Với khả năng của polyphenol này trong việc điều chỉnh nhiều phân tử tín hiệu khác nhau, curcumin đã được báo cáo là có những hoạt động đa diện. Đầu tiên được chứng minh có hoạt động kháng khuẩn vào năm 1949, kể từ đó curcumin đã được chứng minh có tính kháng viêm, chống oxy hóa, kích thích tế bào tự hủy, ngăn ngừa hóa chất, hóa trị liệu, chống tăng trưởng, phục hồi vết thương, giảm đau, chống ký sinh trùng và chống sốt rét. Nghiên cứu trên động vật đã gợi ý rằng curcumin có thể hiệu quả chống lại một loạt bệnh tật ở người, bao gồm tiểu đường, béo phì, các rối loạn thần kinh và tâm thần và ung thư, cũng như các bệnh mạn tính ảnh hưởng đến mắt, phổi, gan, thận và hệ tiêu hóa và tim mạch."

3. Mặc dù đã có nhiều thử nghiệm lâm sàng đánh giá tính an toàn và hiệu quả của curcumin đối với các bệnh tật ở người đã hoàn thành, những thử nghiệm khác vẫn đang tiếp diễn. Hơn nữa, curcumin được sử dụng như một thực phẩm chức năng ở nhiều nước, bao gồm Ấn Độ, Nhật Bản, Mỹ, Thái Lan, Trung Quốc, Hàn Quốc, Thổ Nhĩ Kỳ, Nam Phi, Nepal và Pakistan. Mặc dù giá thành rẻ, có vẻ được dung nạp tốt và có tiềm năng hoạt động, curcumin không được phê duyệt để điều trị bất kỳ bệnh nào ở người."

4. Trong bài báo này, chúng tôi thảo luận về sự phát hiện và các hoạt động sinh học chính của curcumin, với sự nhấn mạnh đặc biệt vào hoạt động của nó ở cấp độ phân tử và tế bào, cũng như ở động vật và con người."

1. A dietary combination of high salt and low potassium (HSLK) exacerbates hypertension in Dahl salt‐sensitive (DS) rats and renders previously normotensive Dahl salt‐resistant (DR) rats hypertensive. In both strains, the severity of hypertension correlates with urinary calcium loss. However, the magnitude of excretory calcium losses is significantly greater in DS rats and is potentiated by chemical sympathectomy in both strains.

2. We hypothesized that a defect in vitamin D metabolism may underlie the observed strain‐dependent differences in calcium balance.

3. Arterial blood pressure (ABP), water and mineral bal‐ ance and serum concentrations of 1,25‐dihydroxyvitamin D₃ (1,25(OH)₂ D₃) and 25‐hydroxyvitamin D₃ (25(OH)D₃) were measured in intact and chemically sympathectomized (6‐hydroxydopamine; 6‐OHDA) DS and DR rats after 8 weeks on a HSLK diet.

4. Chronic ingestion of this diet resulted in marked and moderate levels of hypertension in DS and DR rats, respectively. The hypertension was abated and eliminated by 6‐OHDA in the DS and DR strains, respectively. Independent of treatment, DS rats had significantly higher urinary excretion of calcium and reduced intestinal absorption of the ion compared with DR rats. The DS rats had significantly higher serum levels of 1,25(OH)₂ D₃ and markedly lower serum levels of 25(OH)D₃ than DR rats. Chemical sympathectomy tended to increase 1,25(OH)₂ D₃ and to decrease 25(OH)D₃ levels in both strains.

5. These data indicate a genetic difference in vitamin D metabolism between DS and DR rats. The abnormally elevated levels of 1,25(OH)₂ D₃ in DS rats may be an appropriate compensatory response to excessive excretory calcium loss and reduced target organ sensitivity to the hormone and may, maladaptively, directly contribute to hypertension, by stimulating vascular smooth muscle contractility.

1. The identity of the receptors and afferent nerve fibres that mediate the sense of touch varies somewhat with body location. Those that have been most intensively characterized are associated with the distal glabrous skin of the limbs and, in primates, mediate the sense of touch in the fingertips and palms. In this glabrous skin region, there appear to be three or four principal classes of tactile sensory nerves that fall into two broad groups. One group, the so‐called slowly adapting (SA) receptors and afferent fibres, is responsive to static mechanical displacement of skin tissues and is made up of two classes, the type I (SAI) fibres that innervate Merkel receptors and the type II (SAII) fibres that innervate Ruffini endings. The second broad group displays a pure dynamic sensitivity to tactile stimuli and also falls into two principal classes, the rapidly adapting (RA) tactile fibres that are associated with Meissner corpuscle receptors and the Pacinian corpuscle (PC)‐associated class of tactile afferent fibres.

2. In other regions of the skin, such as the hairy skin of the arms, legs and trunk, there are similar functional classes of tactile sensory nerves, although the receptor endings differ somewhat from those of the glabrous skin.

3. Receptors in close association with the long bones of the limbs include groups of Pacinian corpuscles distributed along the interosseous membranes. These are highly sensitive to dynamic forms of mechanical stimuli, in particular vibrotactile disturbances. However, despite their close association with bone, these receptors probably cannot be legitimately considered ‘osseoreceptors’.

4. Both the periosteum and the bone marrow are richly supplied by nerve fibres. However, much evidence indicates that these are largely or entirely in the fine‐diameter category of nerve fibres, whose roles may be confined to either nociception or to the efferent autonomic regulation of bone‐associated blood vessels.

5. In conclusion, it remains uncertain whether any aspects of our innocuous touch or kinaesthetic senses, in either the limbs or in orofacial regions, can be ascribed to ‘osseoreceptors’ located in the periosteum or within the bone marrow itself.

In a previous study, we demonstrated that heat shock augments the contractility of vascular smooth muscle through the stress response.

1. Hypertension is associated with structural alterations of resistance arteries, a process known as remodelling (increased media‐to‐lumen ratio).

2. At the cellular level, vascular remodelling involves changes in vascular smooth muscle cell (VSMC) growth, cell migration, inflammation and fibrosis. These processes are mediated via multiple factors, of which angiotensin (Ang) II appears to be one of the most important in hypertension.

3. Angiotensin II signalling, via AT₁ receptors, is upregulated in VSMC from resistance arteries of hypertensive patients and rats. This is associated with hyperactivation of vascular NADPH oxidase, leading to increased generation of reactive oxygen species (ROS), particularly O₂^– and H₂O₂.

4. Reactive oxygen species function as important intracellular second messengers to activate many downstream signalling molecules, such as mitogen‐activated protein kinase, protein tyrosine phosphatases, protein tyrosine kinases and transcription factors. Activation of these signalling cascades leads to VSMC growth and migration, modulation of endothelial function, expression of pro‐inflammatory mediators and modification of extracellular matrix.

5. Furthermore, ROS increase intracellular free Ca²⁺ concentration ([Ca²⁺]_i), a major determinant of vascular reactivity.

6. All these processes play major roles in vascular injury associated with hypertension. Accordingly, ROS and the signalling pathways that they modulate provide new targets to regress vascular remodelling, reduce peripheral resistance and prevent hypertensive end‐organ damage.

7. In the present review, we discuss the role of ROS as second messengers in AngII signalling and focus on the implications of these events in the processes underlying vascular remodelling in hypertension.

1. Statins, 3‐hydroxy‐3‐methylglutaryl coenzyme A reductase (HMG‐CoA) inhibitors, exert anti‐inflammatory, anti‐oxidant and anti‐angiogenic effects. These effects are associated with downregulation of pro‐inflammatory/pro‐angiogenic molecules and upregulation of endothelial nitric oxide synthase (e‐NOS) expression/nitric oxide (NO) production.

2. Using the murine sponge model to induce chronic intraperitoneal inflammatory response, we evaluated the inflammatory components, angiogenic and NO production of the fibrovascular tissue, and their modulation by fluvastatin.

3. Our results showed that fluvastatin (0.6 and 6 mg/kg per day) inhibited haemoglobin (Hb) content 4.9 ± 0.4 (n = 15; control) vs 2.2 ± 0.2 (n = 6; fluvastatin 0.6) and 1.8 ± 0.2 (n = 6; fluvastatin 6.0) and the number of vessels in the treated group when compared with the control group. The inflammatory component, as assessed by myeloperoxidase and N‐acetyl‐β‐d‐glucosaminidase activities and by the pro‐inflammatory cytokines, tumour necrosis factor‐α (TNF‐α) and Monocyte chemotactic protein‐1 (MCP‐1)/CCL2/JE levels, was also decreased by the compound. In the treated group, inhibition of both enzyme activities was 54% and 57%, respectively. The levels of the cytokines (TNF‐α and CCL2/JE) intra‐implant were decreased relative to the control. In these implants, fluvastatin was also able to increase NO production, as detected with an NO‐sensitive electrode.

4. The inhibitory function of fluvastatin on key components of intraperitoneal inflammatory angiogenesis shown in the present study is clearly associated with the modulatory effects of this statin on vascular endothelial growth factor, TNF‐α and NO production.

Ferulic acid (FA) is a plant phenolic acid that has several pharmacological effects including antihyperglycaemic activity. Thus, the objective of this study is to investigate the effect of FA on glucose and lipid metabolism in high‐fat diet (HFD)‐induced obese mice. Institute for Cancer Research (ICR) mice were fed a HFD (45 kcal% fat) for 16 weeks. At the ninth week of induction, the obese mice were orally administered with daily FA doses of 25 and 50 mg/kg for the next eight weeks. The results show that FA significantly reduced the elevated blood glucose and serum leptin levels, lowered the insulin resistance, and increased the serum adiponectin level. Moreover, serum lipid level, and liver cholesterol and triglyceride accumulations were also reduced. The histological examination showed clear evidence of a decrease in the lipid droplets in liver tissues and smaller size of fat cells in the adipose tissue in the obese mice treated with FA. Interestingly, FA reduced the expression of hepatic lipogenic genes such as sterol regulatory element‐binding protein 1c (SREBP1c), fatty acid synthase (FAS), and acetyl‐CoA carboxylase (ACC). It could also up‐regulate hepatic carnitine palmitoyltransferase 1a (CPT1a) gene and peroxisome proliferator‐activated receptor alpha (PPARα) proteins. The FA treatment was also found to suppress the protein expressions of hepatic gluconeogenic enzymes, phosphoenolpyruvate carboxylase (PEPCK) and glucose‐6‐phosphatase (G6Pase). In conclusion, the findings of this study demonstrate that FA improves the glucose and lipid homeostasis in HFD‐induced obese mice probably via modulating the expression of lipogenic and gluconeogenic genes in liver tissues.