• Archives of Pharmacal Research
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• 제25권2호
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• pp.184-191
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• 2002

We investigated the role of vitamin C or rutin on neuropathy and lung damage of diabetic mellitus(DM) rats. Norepinephrine content was significantly decreased in sciatic nerves of DM rats compared with non-DM controls but vitamin C had no effect on decreases of norepinephrine. 2,4-dinitrophenylhydrazine (DNPH) incorporation, which is biomarker of protein oxidation, was increased in sciatic nerve of DM rats as compared with normal control. However, vitamin C had no effects on increases of DNPH incorporation . We measured the content of conjugated dienes (CD) as a biomarker of lipid oxidation in sciatic nerve. CD was increased in DM as compared with normal control, Vitamin C or rutin had no effects on increases of CD. However, Rutin plus vitamin C significantly decreased the content of CD as compared with CIM rats. In lung of DM rats, DNPH incorporation or CD was increased as compared with normal control. Vitamin C or Rutin had no effects on increases of CD However, Rutin plus vitamin C significantly decreased the content of DNPH incorporation or CD in lung tissue. Vitamin C caused marked pathological changes such as the increases of parenchyma and the thickening of alveolar septa in the lung of DM. Rutin had protective effects on the pathological changes in the lung of DM rats. In conclusion, Vitamin C had no effects on oxidative parameter, such as DNPH incorporation or CD, and on the decreases of norepinephrine content in DM rats. Vitamin C caused the marked pathological changes in the lung of DM rats but rutin had protective efforts against the pathological changes.

• Journal of Oral Medicine and Pain
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• 제33권4호
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• pp.353-374
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• 2008

비록 신경병성 동통이 환자에게 주는 심리적 부담에 대하여 잘 알고 있지만 동통의 역학조사에 대해서는 아직 잘 알려져 있지 않다. 신경병성 동통의 정확한 발병률도 잘 알려져 있지 않은 데, 이는 여러가지 새로운 의료기기가 개발되었지만 정확한 진단을 하지 못하고 있으며, 적절한 치료를 제대로 하지 못하기 때문이다. 본 연구의 목적은 한국내 모든 종류의 병원에서 치료한 몇 가지 특정 신경병성 동통에 대하여 역학조사를 시행하는 것이다. 2003년 1월부터 2005년 12월까지 건강보험심사평가원(심평원)의 전산에 입력된 환자들을 대상으로 조사한 신경병성 동통 환자와 치료 받은 과 및 치료기간 등에 대하여 조사하였다. 신경병성 동통 환자의 수와 유병률을 살펴보면 삼차신경통 77,053명(27.6%), 비정형적 안면통 12,382명(4.4%), 설인후 신경통 1,319명(0.5%), 포진후 신경통 84,598명(30.3명), 당뇨병성 신경통 85,989명(30.8%), 비정형적 치통 16,001명(5.7%), 설통 2,133명(0.8%) 이며, 시간이 경과함에 따라 포진후 신경통과 당뇨병성 신경통은 증가하는 경향을 보이나, 그 외 신경통은 대부분 증가가 둔화되는 양상을 보였다. 대부분의 환자들은 57.6-72.8% 에 이르도록 1차 의료기관인 개인의원에서 치료받았으나 비정형적 치통의 경우에만 10.3% 정도로 1차 의료기관에서 진료받는 비율이 낮았다. 치과의원에 내원하는 환자의 비율은 삼차신경통 3.2%, 비정형적 치통 35.4%, 설통 15.4%이며 그 외 나머지 신경병성 동통은 대부분 의원에서 치료받았다.

• Diabetes and Metabolism Journal
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• 제42권6호
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• pp.496-512
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• 2018

Background: This study aimed to investigate the association between the presence and severity of cardiovascular autonomic neuropathy (CAN) and development of long-term glucose fluctuation in subjects with type 2 diabetes mellitus. Methods: In this retrospective cohort study, subjects with type 2 diabetes mellitus who received cardiovascular autonomic reflex tests (CARTs) at baseline and at least 4-year of follow-up with ${\geq}6$ measures of glycosylated hemoglobin (HbA1c) were included. The severity of CAN was categorized as normal, early, or severe CAN according to the CARTs score. HbA1c variability was measured as the standard deviation (SD), coefficient of variation, and adjusted SD of serial HbA1c measurements. Results: A total of 681 subjects were analyzed (294 normal, 318 early, and 69 severe CAN). The HbA1c variability index values showed a positive relationship with the severity of CAN. Multivariable logistic regression analysis showed that CAN was significantly associated with the risk of developing higher HbA1c variability (SD) after adjusting for age, sex, body mass index, diabetes duration, mean HbA1c, heart rate, glomerular filtration rate, diabetic retinopathy, coronary artery disease, insulin use, and anti-hypertensive medication (early CAN: odds ratio [OR], 1.65; 95% confidence interval [CI], 1.12 to 2.43) (severe CAN: OR, 2.86; 95% CI, 1.47 to 5.56). This association was more prominent in subjects who had a longer duration of diabetes (>10 years) and lower mean HbA1c (<7%). Conclusion: CAN is an independent risk factor for future higher HbA1c variability in subjects with type 2 diabetes mellitus. Tailored therapy for stabilizing glucose fluctuation should be emphasized in subjects with CAN.

• The Korean Journal of Physiology and Pharmacology
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• 제19권5호
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• pp.401-411
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• 2015

Aldose reductase (AR) is known to play a crucial role in the mediation of diabetic and cardiovascular complications. Recently, several studies have demonstrated that allergen-induced airway remodeling and ovalbumin-induced asthma is mediated by AR. Epalrestat is an aldose reductase inhibitor that is currently available for the treatment of diabetic neuropathy. Whether AR is involved in pathogenesis of pulmonary fibrosis and whether epalrestat attenuates pulmonary fibrosis remains unknown. Pulmonary fibrosis was induced by intratracheal instillation of bleomycin (5 mg/kg) in rats. Primary pulmonary fibroblasts were cultured to investigate the proliferation by BrdU incorporation method and flow cytometry. The expression of AR, TGF-${\beta}_1$, ${\alpha}$-SMA and collagen I was analyzed by immunohistochemisty, real-time PCR or western blot. In vivo, epalrestat treatment significantly ameliorated the bleomycin-mediated histological fibrosis alterations and blocked collagen deposition concomitantly with reversing bleomycin-induced expression up-regulation of TGF-${\beta}_1$, AR, ${\alpha}$-SMA and collagen I (both mRNA and protein). In vitro, epalrestat remarkably attenuated proliferation of pulmonary fibroblasts and expression of ${\alpha}$-SMA and collagen I induced by TGF-${\beta}_1$, and this inhibitory effect of epalrestat was accompanied by inhibiting AR expression. Knockdown of AR gene expression reversed TGF-${\beta}_1$-induced proliferation of fibroblasts, up-regulation of ${\alpha}$-SMA and collagen I expression. These findings suggest that AR plays an important role in bleomycin-induced pulmonary fibrosis, and epalrestat inhibited the progression of bleomycin-induced pulmonary fibrosis is mediated via inhibiting of AR expression.

• Journal of Ginseng Research
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• 제43권1호
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• pp.58-67
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• 2019

Background: Diabetic neuropathy is one of the most devastating ailments of the peripheral nervous system. Neuropathic pain develops in ~30% of diabetics. Here, we examined the suppressive effect of GS-KG9 on neuropathic pain induced by streptozotocin (STZ). Methods: Hyperglycemia was induced by intraperitoneal injection of STZ. Rats showing blood glucose level > 250 mg/dL were divided into five groups, and treatment groups received oral saline containing GS-KG9 (50 mg/kg, 150 mg/kg, or 300 mg/kg) twice daily for 4 wk. The effects of GS-KG9 on pain behavior, microglia activation in the lumbar spinal cord and ventral posterolateral (VPL) nucleus of the thalamus, and c-Fos expression in the dorsal horn of the lumbar spinal cord were examined. Results: The development of neuropathic pain began at Day 5 and peaked at Week 4 after STZ injection. Mechanical and thermal pains were both significantly attenuated in GS-KG9-treated groups from 10 d after STZ injection as compared to those in the STZ control. GS-KG9 also repressed microglia activation in L4 dorsal horn and VPL region of the thalamus. In addition, increase in c-Fos-positive cells within L4 dorsal horn lamina I and II of the STZ control group was markedly alleviated by GS-KG9. Conclusion: These results suggest that GS-KG9 effectively relieves STZ-induced neuropathic pain by inhibiting microglial activation in the spinal cord dorsal horn and VPL region of the thalamus.

• Journal of the Korean Association of Oral and Maxillofacial Surgeons
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• 제45권4호
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• pp.207-214
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• 2019

Objectives: Medically compromised patients often fear required dental surgical procedures that can increase the risk of medical emergency when combined with reduced tolerance for stress. A stress reduction protocol (SRP) helps doctors minimize treatment-related stress and improves patient management with minimum complications. Diabetes and co-morbid hypertension carry 4-fold risk of aggravation of cardiovascular emergencies and 7.2-fold risk of mortality. Diabetic neuropathy can result in difficult diagnosis of myocardial infarction and reduces chances of surviving a myocardial infarction compared with a non-diabetic person. The aim of the study was to assess the feasibility of a protocol for management of patients having both diabetes and hypertension who required minor oral surgery to minimize the rate of cardiovascular emergencies. Materials and Methods: A prospective study was conducted in 140 patients having both diabetes and hypertension who required minor oral surgical procedures. A systematic approachable protocol was designed for management of such patients. Results: Among 140 patients, 6 patients (4.3%) had cardiovascular complications, while 3 patients (1 with syncope and 2 with hypertension) did not require any intervention other than observation. Two patients were managed with aspirin and nitroglycerin, and 1 patient had possible myocardial infarction (overall incidence 0.7%) with chest pain, S-T segment elevation on electrocardiogram, and troponin level of 0.60 ng/mL. Conclusion: The proposed protocol helps to improve management of patients having both diabetes and hypertension. We recommend that patients with uncontrolled diabetes and uncontrolled hypertension and/or patients having history of cardiovascular complication should be treated in a medical facility with a readily available cardiology unit. This facilitates prompt response to emergency and instant implementation of treatment, helping to reduce morbidity and mortality.

• The Korean Journal of Medicine
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• 제99권4호
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• pp.210-218
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• 2024

목적: 자율신경계 합병증과 같은 당뇨 합병증을 갖고 있는 환자들에게 있어 위장관계 증상은 매우 흔한 편이다. 그러나 당뇨 합병증이 발병하기 전에 위장관계 증상의 유병률이 어떤지는 명확히 알려져 있지 않다. 방법: Rome III 기준에 의거해 내분비내과를 찾은 환자들에게 기능성 위장장애에 관한 증상 설문조사를 실시하였다. 조사 영역은 기능성 소화 불량과 과민성 대장증후군, 기능성 변비에 관련된 질문들로 구성하였다. 결과: 당뇨 전단계, 당뇨병성 신경병증을 가지고 있지 않은 당뇨병 환자들, 당뇨병성 신경병증을 가진 당뇨병 환자군에 있어서 기능성 위장장애의 유병률은 각각 기능성 소화 불량의 경우 16.52%, 27.27% 그리고 23.53%, 과민성 대장증후군의 경우 8.70%, 11.68% 그리고 16.81%, 기능성 변비의 경우 8.85%, 11.85% 그리고 15.25%로 확인되었다. 하위 분류분석에서 식후 포만감과 조기 만복감과 같은 증상을 보이는 식후고통증후군의 유병률이 명치통증증후군보다 좀 더 높게 확인되었다. 기능성 변비에 관련된 하위 분류 분석에 있어 항문직장 폐쇄감이 있거나 배변을 돕기 위한 부가 처치가 필요한 경우와 같은 골반 출구 폐쇄 증상의 유병률이 서행성 변비 증상의 경우보다 더 높게 확인되었다. 결론: 기능성 위장장애의 유병률은 전반적으로 당뇨병이 더 심해짐에 따라 더욱 증가한다. 하지만 당뇨병과 연관된 위장관계 증상은 그 합병증이 발생하기 오래전부터 발생하게 된다. 따라서 이를 미리 확인하여 적절한 치료와 조치를 취할 필요가 있겠다.

• Biomolecules & Therapeutics
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• 제5권2호
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• pp.150-157
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• 1997

Capsaicin cream has been used to attenuate the pain associated with diabetic neuropathy, rheum-atoid arthritis, osteoarthritis and postherpetic neuralgia. But its common side effect, local irritation, limits the use of it and there is still a need for a new analgesic devoid of this side effect. This study was conducted to compare the local irritant effect of DA-5018, a new capsaicin derivative, with that of capsaicin in various animal models and human beings. Capsaicin, applied topically to the mouse ear, produced dose-dependent increase of ear volume and the frequency of ear scratching behavior in mice. Neither ear volume nor scratching behavior was affected by DA-5018. In eye wiping test of rat, DA-5018 was 10 times less irritant than capsaicin. Capsaicin administered intradermally into the rat paw elicited paw lick/lift response with a potency which was three times that of DA-5018. Zostrix-HP (0.075% capsaicin cream), but not DA-50180.3% cream, increased ear volume of rat and induced thermal hyperalgesia in normal and carrageenan inflamed paws. Six day-treatment of Zostrix-HP failed to develop tolerance against this thermal hyperalgesia. In human beings, Zostrix-HP produced burning sensation and itching in more than 90% of volunteers involved and its maximum irritant effect was significantly higher than that of DA-5018 cream. These results suggest that local irritation and burning sensation produced by DA-5018 is much less than capsaicin.

• 약학회지
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• 제44권6호
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• pp.539-544
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• 2000

Many diabetic patients develop serious complications during the course of the disease, including cardiovascalar disorders, nepropathy, neuropathy and retinopathy. Because some physiological changes occurring in diabetes mellitus patients could alter the pharmacokinetics of drugs used to treat the disease, the pharmacokinetics of gentamycin was investigated after intravenous administration (2 mg/kg) to control rabbits and acute or chronic alloxan-induced diabetes mellitus rabbits (AIDRs). After intravenous administration, the serum concentrations of gentamycin were significantly higher between 6 and 12 hr in chronic AIDRs compared with those in control rabbits. The AUC was significant greater in chronic ($31.91\;{\pm}\;3.76\;{\mu}g/ml{\cdot}hr$) AIDRs than that in control ($21.60\;{\pm}\;2.45\;{\mu}g/ml{\cdot}hr$) rabbits. Total body clearance (CLt) in AIDRs were significantly decreased compared with that in control rabbits. Cumulative urinary excretion of gentamycin was decreased, although not significantly, in AIDRs compared with that in control rabbits.

• 대한핵의학회지
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• 제38권5호
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• pp.331-337
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• 2004

Cardiac neurotransmission imaging allows in vivo assessment of presynaptic reuptake, neurotransmitter storage and postsynaptic receptors. Among the various neurotransmitter, I-123 MIBG is most available and relatively well-established. Metaiodobenzylguanidine (MIBG) is an analogue of the false neurotransmitter guanethidine. It is taken up to adrenergic neurons by uptake-1 mechanism as same as norepinephrine. As tagged with I-123, it can be used to image sympathetic function in various organs including heart with planar or SPECT techniques. I-123 MIBG imaging has a unique advantage to evaluate myocardial neuronal activity in which the heart has no significant structural abnormality or even no functional derangement measured with other conventional examination. In patients with cardiomyopathy and heart failure, this imaging has most sensitive technique to predict prognosis and treatment response of betablocker or ACE inhibitor. In diabetic patients, it allow very early detection of autonomic neuropathy. In patients with dangerous arrhythmia such as ventricular tachycardia or fibrillation, MIBG imaging may be only an abnormal result among various exams. In patients with ischemic heart disease, sympathetic derangement may be used as the method of risk stratification. In heart transplanted patients, sympathetic reinnervation is well evaluated. Adriamycin-induced cardiotoxicity is detected earlier than ventricular dysfunction with sympathetic dysfunction. Neurodegenerative disorder such as Parkinson's disease or dementia with Lewy bodies has also cardiac sympathetic dysfunction. Noninvasive assessment of cardiac sympathetic nerve activity with I-123 MIBG imaging nay be improve understanding of the pathophysiology of cardiac disease and make a contribution to predict survival and therapy efficacy.