Smoking is associated with insulin resistance and cardiovascular autonomic dysfunction in type 2 diabetic patients

BACKGROUND: Smoking and cardiovascular autonomic dysfunction are associated with high mortality in type 2 diabetic patients. This study tested the hypothesis that smoking is associated with insulin resistance/hyperinsulinaemia and cardiovascular autonomic dysfunction in type 2 diabetic patients who are not treated with insulin. MATERIALS AND METHODS: The study patients were 22 current smokers with type 2 diabetes mellitus (age: 57 +/- 5 years, mean +/- SD) and 30 age-matched never-smoked patients with type 2 diabetes mellitus (control group, 57 +/- 8 years). The quality of blood glucose was assessed by fasting plasma glucose (FPG), fasting immunoreactive insulin (F-IRI), homeostasis model assessment (HOMA) index and haemoglobin A1c (HbA1c). The severity of smoking status was expressed by the Brinkman index, which is calculated as number of cigarettes per day multiplied by years of smoking. Cardiovascular autonomic function was assessed by baroreflex sensitivity (BRS), heart-rate variability, plasma norepinephrine concentration and cardiac (123)I-metaiodobenzylguanidine (MIBG) scintigraphic findings. RESULTS: Baroreflex sensitivity was lower in the current smokers group than in the never-smoked group (P < 0.05). Early and delayed (123)I-MIBG myocardial uptake values were lower (P < 0.05, and P < 0.01, respectively) and the percentage washout-rate of (123)I-MIBG was higher (P < 0.0001) in the current smokers group than in the never-smoked group. Fasting immunoreactive insulin (F-IRI) concentration (P < 0.0001) and the homeostasis model assessment (HOMA) index (P < 0.0001) were higher in the current smokers group than the never-smoked group. Multiple logistic regression analysis revealed that smoking was independently predicted by F-IRI and the percentage washout-rate of (123)I-MIBG. CONCLUSIONS: The results of the study suggested that smoking was associated with cardiovascular autonomic dysfunction and hyperinsulinaemia and that F-IRI and the percentage washout-rate of (123)I-MIBG were independent predictors of smoking in these Japanese patients with type 2 diabetes mellitus.     

Potential risk factors for psychiatric disorders in patients with headache

Background.— Psychiatric comorbidities are common among patients with headache. These can compromise the quality of life of patients and may affect the result of treatment. No available systematic study concerning this problem has been conducted in Thailand. Objective.— The study aimed to determine the prevalence and risk factors of psychiatric disorders in patients with headache in tertiary care facility. Methods.— The study was conducted at the Headache Clinic, King Chulalongkorn Memorial Hospital in Bangkok, Thailand. One hundred and thirteen patients were enrolled. Diagnosis of headache was made based on International Classification of Headache Disorders II system. Mental disorders were assessed using Primary Care Evaluation of Mental Disorders. Other possible risk factors were extracted using significant physical symptoms count and accumulated risk for mental disorder. Results.— Of the 113 samples analyzed, the prevalence of depression, anxiety, and somatoform disorder was found to be 29.2%, 9.7%, and 27.4%, respectively. No definite relationship between headache types and mental disorders was observed. High number of significant physical complaints and health concerns significantly increased the risk for depression (OR = 4.6, 95% CI = 1.6 to 13.5) while the level of possible risk for mental disorder was associated with an increased risk for somatoform disorder (OR = 1.6, 95% CI = 1.2 to 2.2). Conclusion.— The study confirmed high prevalence of psychiatric comorbidities in patients with headache. The results of this study will raise the awareness of physicians to possible underlying mental disorders in patients with headache and facilitate appropriate treatment or psychiatric referral.     

Brain-state-independent neural representation of peripheral stimulation in rat olfactory bulb

It is critical for normal brains to perceive the external world precisely and accurately under ever-changing operational conditions, yet the mechanisms underlying this fundamental brain function in the sensory systems are poorly understood. To address this issue in the olfactory system, we investigated the responses of olfactory bulbs to odor stimulations under different brain states manipulated by anesthesia levels. Our results revealed that in two brain states, where the spontaneous baseline activities differed about twofold based on the local field potential (LFP) signals, the levels of neural activities reached after the same odor stimulation had no significant difference. This phenomenon was independent of anesthetics (pentobarbital or chloral hydrate), stimulating odorants (ethyl propionate, ethyl butyrate, ethyl valerate, amyl acetate, n-heptanal, or 2-heptanone), odor concentrations, and recording sites (the mitral or granular cell layers) for LFPs in three frequency bands (12-32 Hz, 33-64 Hz, and 65-90 Hz) and for multiunit activities. Furthermore, the activity patterns of the same stimulation under these two brain states were highly similar at both LFP and multiunit levels. These converging results argue the existence of mechanisms in the olfactory bulbs that ensure the delivery of peripheral olfactory information to higher olfactory centers with high fidelity under different brain states.     

Management of gastrointestinal complications in hereditary transthyretin amyloidosis: a single-center experience over 40 years

Introduction: Hereditary transthyretin amyloidosis (ATTRm amyloidosis) is a rare disease caused by the deposition and accumulation of insoluble non-native transthyretin fibrils in the body. The disease inevitably results in widespread organ disruption, and poor life expectancy. The GI tract is one organ system vulnerable to disruption and, although the clinical presentation of the disease varies, GI involvement affects most patients with ATTRm amyloidosis.

Areas covered: This article presents our experience with diagnosing and treating the GI symptoms of ATTRm amyloidosis patients at our center over the last 40 years, in the Swedish clustering area of the disease. Our aim is to help other physicians to better manage GI complications in patients with this rare but widespread condition.

Expert commentary: GI symptoms are debilitating complications for ATTRm amyloidosis patients to experience, yet with the appropriate questioning and diagnosis methods, symptomatic treatments of these symptoms can be implemented to provide relief. Further, patients with fewer GI complications and a good nutritional status are also better candidates for liver transplantation which, in selected cases, is the best disease-modifying treatment of ATTRm amyloidosis to date.     

Upstaging to invasive ductal carcinoma after mastectomy for ductal carcinoma in situ: predictive factors and role of sentinel lymph node biopsy

Background

The aim of this study was to investigate preoperative factors associated with ductal carcinoma in situ (DCIS) upstaged to invasive ductal carcinoma (IDC) and sentinel lymph node (SLN) status in patients who underwent mastectomy for a preoperative diagnosis of DCIS.

Methods

The medical records of 220 patients who underwent mastectomy for a preoperative diagnosis of DCIS were retrospectively reviewed.

Results

Fifty-one (22.6%) of 226 lesions were upgraded to IDC after mastectomy. Preoperative factors associated with upstaging to IDC included patient-reported signs and symptoms, a clinically palpable mass, ultrasound findings classified as category 4 or 5, the ultrasound appearance of a mass or widely distributed non-mass abnormality (NMA), and a high Ki67 index. The prevalence of SLN macrometastasis was 0.9%. IDC was diagnosed for 10.9% of lesions of a preoperative ultrasound category of 0–3, 13.0% of those with no mass or NMA detected by ultrasonography, and 14.1% of lesions preoperatively diagnosed by methods other than core needle biopsy (CNB). Of those lesions, none was associated with SLN metastasis.

Conclusions

Routinely performing SLN biopsy for patients undergoing mastectomy for a preoperative diagnosis of DCIS is overtreatment, because the prevalence of SLN metastasis was low. SLN biopsy can be omitted for most patients. In particular, we suggest omitting SLN biopsy for patients who have lesions of ultrasound category 0–3, who have neither a mass nor NMA detected by ultrasound, or whose initial diagnosis was made based on a specimen obtained by methods other than CNB.

     

Carbazole alkaloids from <Emphasis Type="Italic">Murraya koenigii</Emphasis> trigger apoptosis and autophagic flux inhibition in human oral squamous cell carcinoma cells

Carbazole alkaloids, a major constituent of Murraya koenigii (L.) Sprengel (Rutaceae), exhibit biological effects such as anticancer activity via the induction of apoptosis, and they represent candidate chemotherapeutic agents. Oral squamous cell carcinoma (OSCC) is the most prevalent cancer of the oral cavity and a growing and serious health problem worldwide. In this study, we investigated the anticancer properties and mechanisms of action of two carbazole alkaloids derived from M. koenigii leaves, mahanine and isomahanine, in the OSCC cell line CLS-354. At 15 μM, mahanine and isomahanine were cytotoxic to CLS-354 cells, triggering apoptosis via caspase-dependent and -independent mechanisms. Autophagosomes, visualised using monodansylcadaverine (MDC) labelling, were numerous in carbazole alkaloid-treated cells. Mahanine and isomahanine markedly induced the expression of the autophagosome marker microtubule-associated protein 1 light chain 3, type II (LC3B-II). Genetic and chemical inhibition of autophagy via silencing of the Autophagy protein 5 gene and exposure to bafilomycin A1 (BafA1), respectively, did not arrest carbazole alkaloid-induced apoptosis, indicating that it occurs independently of autophagic activation. Surprisingly, both carbazole alkaloids caused increased accumulation of p62/sequestosome1 (p62/SQSTM1), with coordinated expression of LC3B-II and cleaved caspase-3, suggesting inhibition of autophagic flux. Our results suggest that inhibition of autophagic flux is associated with carbazole alkaloid-induced apoptosis. Our findings provide evidence of a novel cytotoxic action of natural carbazole alkaloids and support their use as candidate chemotherapeutic agents for the treatment of OSCC.     

Lipoprotein (a) as a risk factor for silent cerebral infarction in hemodialysis patients

In patients with chronic renal failure undergoing hemodialysis (HD), silent cerebral infarctions (SCIs) are associated with high mortality. Levels of lipoprotein (a) (Lp[a]) increase with renal dysfunction and may be a novel predictor for cerebrovascular events. We tested the hypothesis that increased Lp(a) levels correlate with the occurrence of SCI in HD patients. Using cranial magnetic resonance imaging findings, we divided 62 Japanese patients undergoing HD into with-SCI group (61 ± 7 years, mean ± SD, n = 34) and without-SCI group (60 ± 6 years, n = 28). We compared the sex, body mass index, metabolic profiles, Lp(a) levels, and smoking habits between the 2 groups. The following observations were noted: (1) The number of patients with diabetes or hypertension did not differ between the 2 groups. (2) The levels of Lp(a) were higher in the with-SCI group in comparison with the without-SCI group (P < .0001). (3) The proportion of smokers was higher in the with-SCI group than in the without-SCI group (P < .05). (4) Plasma levels of high-density lipoprotein cholesterol were lower, whereas uric acid was higher, in the with-SCI group than in the without-SCI group (P < .001 and P < .05, respectively). (5) Multiple logistic regression analysis identified Lp(a) levels as being significantly associated with the presence of SCI (odds ratio, 1.23; 95% confidence interval, 1.09-1.38; P < .0001). This study indicates that patients with chronic renal failure, who are maintained on HD, exhibit an increased prevalence of SCI and that Lp(a) is significantly associated with the presence of SCI in HD patients.     

Retinol binding protein 4 concentrations are influenced by renal function in patients with type 2 diabetes mellitus

Retinol binding protein 4 (RBP-4), a newly discovered adipocytokine, has been involved in glucose and lipid metabolism. We assess the impacts of renal function on plasma RBP-4 levels in patients with type 2 diabetes mellitus with a wide range of nephropathy. Plasma RBP-4 levels were measured using the enzyme immunoassay method in 38 type 2 diabetes mellitus patients with nephropathy and were compared with those in 20 patients with normoalbuminuria. The levels of plasma RBP-4 were increased by 1.4- and 3.3-fold in patients with renal disease with macroalbuminuria (P = .04) and end-stage renal disease (plasma creatinine level >2.0 mg/dL) (P < .0001) compared with those in patients with normal renal function. In addition, RBP-4 levels were correlated with the creatinine level and 24-hour creatinine clearance (Ccr) on simple and multiple regression analyses in all patients. Furthermore, in patients having Ccr of more than 60 mL/min, RBP-4 levels were correlated with the homeostasis model assessment (HOMA)-r index and triglyceride (TGL) both on simple and multiple regression analyses. Interestingly, in patients having Ccr of less than 60 mL/min, RBP-4 levels were not correlated with the HOMA-r index and TGL on simple regression analysis. The RBP-4 concentrations are influenced by renal function in type 2 diabetes mellitus patients. In addition, RBP-4 levels were correlated with HOMA-r and TGL in diabetic subjects without end-stage renal disease.