Effects of tangshenkang capsule on diabetic nephropathy

To study the effects of Chinese herbal medicine Tangshenkang (TSK) capsule on diabetic nephropathy (DN), 57 patients with DN were randomly divided into two groups, the treated group and the control group, they were treated with TSK capsule and the conventional therapy respectively. There were serious disorders of metabolism in DN patients, that showed the TXB 2/6-keto-PGF1 alpha ratios and lipid peroxidase (LPO) levels were higher than that of healthy people. After 6 weeks treated with TSK capsule the albuminuria levels reduced obviously (decreased 51%), renal plasma flow (RPF) increased, glomerular filtration rate and the LPO levels decreased and a positive correlation was observed between albuminuria levels and TXB 2/6-keto-PGF1 alpha ratios while the clearance rate of creafinin didn't improve significantly. There were no significant difference in the above-mentioned parameters in the control group before and after treatment. These results suggested that TSK capsule possessed a significant effect in improving albuminuria and glomerular function. And the effect of TSK might be due to its adjusting TXB 2/6-keto-PGF1 alpha ratios and its lipid-peroxidation in DN patients.     

Nitric oxide synthase inhibition in a spontaneously hypertensive rat model of diabetic nephropathy

Squamous odontogenic tumour is a benign odontogenic tumour composed of a well-differentiated squamous epithelium immersed in a fibrous connective tissue stroma. It is a rare tumour and a recent literature review yielded only 36 cases. Two cases of squamous odontogenic tumour are presented, 1 located in the maxilla and the other in the mandible: 1 of these cases showed a periodontal involvement. The radiographic picture was fairly characteristic in 1 case, with a radiolucent lesion between the roots of the second mandibular premolar and the first molar, while, in the other case, it was possible to observe the presence of a lesion located at the apex of a molar. The tumours were enucleated, and no recurrences were observed after 5 years.     

The clinical course of diabetic nephropathy

A retrospective record analysis of 112 juvenile-onset diabetics with nephropathy was conducted in order to determine their clinical course. The mean duration of diabetes at the onset of proteinuria was 17.3+/-6.0 years. Early renal failure appeared two years after the onset of protein-uria, and severe renal failure (mean serum creatinine level, 8.5+/-3.9 mg/100 ml) four years after the onset of proteinuria. The mean duration of life after the onset of severe renal failure was six months. The mortality was 53%, with 59% of the deaths attributable to renal failure and 36% to cardiovascular disease. All patients experienced progressive deterioration of renal function as well as the other complications of diabetes, the rate of progression being accelerated toward the end of the course. Juvenile onset diabetics should be considered for renal transplantation before the serum creatinine level reaches 8.5 mg/100 ml.     

Care of patients with diabetic nephropathy

Diabetic nephropathy is one of the main causes of chronic renal failure in developed countries. The genesis and development of diabetic nephropathy is associated in both types of diabetes with a more rapid progression of other secondary complications and an increased mortality, in particular cardiovascular mortality. The main causes of development of diabetic nephropathy are prolonged hyperglycaemia along with a so far not elucidated inborn disposition. The course of diabetic nephropathy is characterized more clearly in type 1 diabetes. The clinically manifest stage is already irreversible and in the course of years it develops into chronic renal failure. Preventive and curative measures include maintenance of optimal metabolic control, systematic control of blood pressure, in particular by ACE-inhibitors, and a reduction of protein intake. Systematic multidisciplinary collaboration in care for patients with diabetic nephropathy helps to prevent the progression of other secondary complications such as diabetic foot and diabetic retinopathy. At present in the Czech Republic dialysis methods substituting renal function are available to practically all patients with diabetic nephropathy. As regards survival time and quality of life the optimal method of renal function replacement for patients in the terminal stage of diabetic nephropathy is transplantation.     

Treatment of arterial hypertension in diabetic nephropathy. Certainties and hypotheses

Clinical observation has long emphasized the importance of arterial hypertension in the course of diabetic nephropathy and recent studies suggest that hypertension might play a decisive pathogenetic role in the course of the disease, hence the necessity of correcting the hypertension of diabetic patients has by now been universally accepted. There is, however, still some uncertainty concerning the usefulness of acting preventively on so-called microhypertension; in other words, whether early antihypertensive drug treatment can prevent diabetic nephropathy. This paper discusses the criteria to be followed in the choice of antihypertensive medication during diabetic nephropathy giving special attention to pathophysiological considerations. Moreover, it also discusses the effects of antihypertensive drugs currently regarded as first-choice agents, i.e. calcium antagonists and the angiotensin converting enzyme inhibitors, on intrarenal hemodynamics.     

Potential role of TGF-beta in diabetic nephropathy

Renal injury in diabetes mellitus is a major cause of morbidity and mortality. Several manifestations of diabetic nephropathy may be a consequence of altered production and/or response to cytokines or growth factors. Transforming growth factor-beta (TGF-beta) is one such factor because it promotes renal cell hypertrophy and regulates the production of extracellular matrix molecules. In addition, high ambient glucose increases TGF-beta1 mRNA and protein level in cultured proximal tubular cells and glomerular epithelial and mesangial cells. Neutralizing anti-TGF-beta antibodies or antisense TGF-beta1 oligodeoxynucleotides prevents the hypertrophic effects of high glucose and the stimulation of matrix synthesis in renal cells. Several reports have described overexpression of TGF-beta in the glomeruli and tubulointerstitium of experimental and human diabetes mellitus. We recently provided evidence that the kidney in diabetic patients displays net renal production of immunoreactive TGF-beta1, whereas there is net renal extraction in nondiabetic subjects. We also demonstrated that short-term treatment of streptozotocin-diabetic mice with neutralizing monoclonal antibody directed against TGF-beta significantly reduces kidney weight and glomerular hypertrophy, and attenuates the increase in extracellular matrix mRNA levels. The factors that mediate increased renal TGF-beta activity involve hyperglycemia per se and the intermediary action of other potent mediators such as angiotensin II, thromboxane, endothelins, and platelet-derived growth factor.     

DNA polymorphisms in the ACE gene, serum ACE activity and the risk of nephropathy in insulin-dependent diabetes mellitus

BACKGROUND: To determine the relationship between DNA polymorphisms in the angiotensin I converting enzyme (ACE) gene, serum ACE activity and the risk of diabetic nephropathy. METHODS: A case-control study was carried out in a population of Jewish insulin-dependent diabetes mellitus (IDDM) patients. Cases (77 IDDM patients with diabetic nephropathy) and controls (89 IDDM patients with normoalbuminuria) were genotyped with PCR protocols for detecting two DNA polymorphisms in the ACE gene: one in intron 7 detected with the restriction enzyme PstI and the other in intron 16 identified as an insertion/deletion (I/D). RESULTS: The risk of nephropathy was increased only in patients homozygous for the allele with the PstI site. These homozygotes had a nephropathy risk that was 2.3 times (95% C.I.: 1.2-4.5) that of the other genotypes. Furthermore, these individuals did not have elevated serum ACE activity. CONCLUSIONS: The results of this study are evidence that the risk of diabetic nephropathy in IDDM is influenced by genetic variability at the ACE locus, but the responsible variant is not the I/D polymorphism in intron 16. Our findings require further studies in other populations.     

Effects of dopamine synthesis inhibition on WAIS Comprehension.

A previous study has shown that parkinsonian patients treated with levodopa had decreased scores over time on the Comprehension subtest of the WAIS, whereas scores on all other 10 subtests of the WAIS increased. It was hypothesized that if levodopa treatment, which increases dopamine activity in the brain, is directly related to an apparent deleterious effect on the WAIS Comprehension, then a drug such as alpha-methylparatyrosine (AMPT), which decreases dopamine activity, might have an augmenting effect on this subtest. A therapeutic trial of AMPT in a group of 9 19–35 yr old chronic schizophrenic patients provided an opportunity to test this hypothesis. Comprehension scores improved significantly with AMPT. Other clinical rating instruments failed to show any changes. Implications of using a psychometric instrument to assess specific, but clinically obscured, drug effects on intellectual functioning are discussed. (19 ref) (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

High incidence of diabetic nephropathy in early-onset Japanese NIDDM patients. Risk analysis

OBJECTIVE: Because early-onset Japanese NIDDM patients (diagnosed before age 30 years) can develop diabetic end-stage renal failure (ESRF) in their thirties, this study was performed to elucidate the incidence and determinants for the development of diabetic nephropathy. RESEARCH DESIGN AND METHODS: The incidence of diabetic nephropathy and its relationship to baseline characteristics and long-term metabolic control were determined in 426 early-onset Japanese NIDDM patients who were followed for a mean of 6.8 years. RESULTS: Of these 426 patients, 41 developed diabetic nephropathy manifested by persistent proteinuria (incidence rate [95%CI]/1,000 person-years; 14.1 [10.4-19.1]). Among patients whose mean HbA1c (measured by a high-performance chromatography method that is standardized and comparable to the one used in the Diabetes Control and Complications Trial study) was around 7% or less, few developed nephropathy. The incidence of nephropathy increased with increasing mean HbA1c level in a dose-dependent manner (chi 2 trend = 49.9, P < 0.0001). Diastolic blood pressure and duration of diabetes at entry had significant predictive effects independent of metabolic control. CONCLUSIONS:The incidence rate of diabetic nephropathy in early-onset Japanese NIDDM patients is potentially high, similar to or higher than that in Pima Indian NIDDM or Caucasian IDDM patients of comparable age. Diabetic nephropathy in NIDDM patients aged in their thirties or forties is likely to be an early feature that leads to ESRF, and this would contribute to the marked increase in the number of new patients with diabetic ESRF in Japan. NIDDM is a serious disease if near-normal glycemia is not achieved.     

Effects of ACE inhibitor on renal anemia in predialysis patients

Enterocolitis necroticans or pigbel is a rare condition characteristically affecting chronically malnourished people who abruptly increase their intake of protein. The classic presentation of the disease as seen in the highlands of Papua New Guinea is that of a necrotising enterocolitis after the ritual ingestion of contaminated pork. In this context, the presentation of the same disease in a well nourished white vegetarian in Oxford was all the more intriguing.     

How I evaluate...diabetic nephropathy. First part: micro- and macroalbuminuria

Diabetic nephropathy (DN) appears in about 30% of patients with type 1 diabetes (D1) and 15 to 60% of patients with type 2 diabetes (D2). It is preceded by microalbuminuria. Microalbuminuria is defined as an albumin excretion rate between 30 and 300 mg/24 h (on a 24-hour urine collection) or between 20 and 200 micrograms/min (on an overnight collection) in at least two out of three consecutive collections made within a 6-month period. Alternative screening techniques use either dipstick (Micral-Test II) or the albumin to creatinine ratio on an early morning urine sample (30-300 mg/g creatinine). Once persistent microalbuminuria is confirmed, 80% of type 1 diabetic patients and 20 to 50% of type 2 diabetic patients will progress to DN. In D2, microalbuminuria also represents a powerful predictor of early mortality from cardiovascular disease. Macroalbuminuria (AER > 300 mg/24 h, corresponding to a total protein excretion > 500 mg/24 h) will eventually lead to a end-stage renal insufficiency within 10 to 20 years. In D2, numerous patients will die from cardiovascular disease before reaching end-stage renal failure. Angiotensin-converting enzyme inhibitors can slow down the evolution toward DN when prescribed when microalbuminuria appears. Screening for microalbuminuria should therefore be a part of the annual clinical assessment in every diabetic patient.     

How I examine...diabetic nephropathy. Second part: assessment of glomerular filtration

This study was conducted to determine the uptake of dihydroergotamine (DHE) into the brain after intravenous and intranasal administration in rats. Eight anesthetized rats received either an intravenous (i.v.) or two successive intranasal (i.n.) doses of tritium labeled dihydroergotamine (3H-DHE) with 14C-inulin as a non-BBB (blood-brain barrier) permeable marker. Radioactivity concentrations in plasma were determined at designated times within 30 min postdose, and in blood and seven brain regions (olfactory bulb, frontal cortex, parietal cortex, occipital cortex, cerebellum, mid-brain areas, and brain stem) at 30 min. The plasma-to-brain permeability*area product (PeA) following an i.v. dose was calculated based on the 30-min brain tissue concentration and the area under the plasma concentration-time curve (AUC0-30 min, i.v.) assuming unidirectional transport from plasma to brain. Direct transport from nasal cavity to brain was assessed based on the amount of radioactivity in brain determined experimentally and predicted based on plasma AUC0-30 min, i.n. and PeA obtained from i.v. data. Following an i.v. dose, DHE distributed into the brain with a brain-to-plasma concentration ratio of approximately 5% at 30 min postdose. The PeA value of DHE ranged from 8.6 x 10(-4) to 37.5 x 10(-4) mL min(-1) g(-1) in different brain regions. Following i.n. doses the experimentally determined concentration in olfactory bulb was approximately 51 times, and in other regions three to seven times, greater than predicted values based only on PeA and plasma AUC, suggesting a direct transport pathway from the nasal cavity to the brain. As a result, the brain tissue concentrations at 30 min were similar to (0.31-1.04 times) those following an i.v. dose except for the olfactory bulb, in which the concentration was approximately four times greater than that following an i.v. dose. In conclusion, 3H-DHE penetrated the BBB following intravenous administration. Following i.n. doses, 3H-DHE was able to enter the brain directly from the nasal cavity, with the olfactory bulb being a part of the direct passage from nasal cavity to brain.     

Effect of chronic growth hormone administration on diabetic nephropathy in the rat

Indirect data exist which implicate elevated growth hormone (GH) as a factor in the development of diabetic nephropathy. The administration of somatostatin (SRIH) has been shown to reverse many of the changes found in early diabetic nephropathy; however, it is unknown whether SRIH causes these effects by the suppression of GH or by other unspecified factors. To study directly the possible effect of excess GH in the development of diabetic nephropathy, either ovine growth hormone (0.2 mg oGH) or diluent buffer was administered IM daily for 19 weeks to diabetic rats and to controls. Severity of nephropathy was assessed by 24 hour urine albumin excretion (UAE), relative kidney weight, and kidney histology. Results showed that diabetic rats overall had elevated UAE and kidney weight vs non-diabetic rats (46.2 +/- 8.6 vs 5.4 +/- 1.3 mg per day and 5.7 +/- 0.2 vs 2.7 +/- 0.1 mg per g of body weight, respectively, p < 0.001). However, no differences were detected between diabetic rats treated with GH compared to control diabetic rats. Additionally, diabetic rats had histopathologic changes consistent with early diabetic nephropathy, but no difference in severity scores was found between diabetic groups. These data provide evidence against GH as an etiologic factor in the development of diabetic nephropathy and it is speculated by the authors that SRIH exerts its protective renal effects in diabetes by mechanisms other than GH suppression.     

Preventing diabetic nephropathy: the role of primary care

Diabetic nephropathy is the leading cause of end-stage renal disease in the United States and is associated with significant human and economic cost. It is recognized that care of the person with diabetes should be focused on the prevention of the many devastating long-term complications of the disease. The primary care provider is in a key position to implement good preventive care. Monitoring for microalbuminuria is the accepted method for identifying early nephropathy. Individual providers need to be aware of current guidelines for performing screening exams. Once early nephropathy is detected, prudent care with tight glycemic control, angiotension-converting enzyme therapy, control of hypertension, and lifestyle risk-factor modification are warranted. Currently, there is strong indication that the progression of renal disease can be slowed with appropriate early interventions. Positive outcomes are dependent on timely detection of microalbuminuria.