Low concentrations of amitriptyline inhibit nicotinic receptors in unmyelinated axons of human peripheral nerve

Background and purpose:

Amitriptyline is often prescribed as a first-line treatment for neuropathic pain but its precise mode of analgesic action remains uncertain. Amitriptyline is known to inhibit voltage-dependent ion channels and also to act as an antagonist at ligand-gated ion channels, such as nicotinic acetylcholine receptors (nAChRs). In the present study, we tested the effect of amitriptyline on nicotinic responses of unmyelinated axons in isolated segments of human peripheral nerve. In particular, a comparison was made between the concentrations of amitriptyline necessary for inhibition of nAChRs and those required for inhibition of the compound C-fibre action potential.

Experimental approach:

Isolated axon fascicles were prepared from short segments of human sural nerve, and multiple measures of axonal excitability were recorded using computer-controlled threshold tracking software.

Key results:

Amitriptyline (EC₅₀ 2.6 µM) reduced the nicotine-induced increase in C-fibre excitability but only slightly altered the amplitude and latency to onset of the compound action potential. In contrast, tetrodotoxin produced a clear reduction in the amplitude and a prolongation of action potential onset latency but was without effect on the nicotine-induced increase in axonal excitability.

Conclusions and implications:

These data demonstrate that low concentrations of amitriptyline suppress the response of human peripheral C-type axons to nicotine by directly inhibiting nAChRs. Blockade of tetrodotoxin-sensitive, voltage-dependent sodium channels does not contribute to this effect. An inhibitory action of amitriptyline on nAChRs in unmyelinated nociceptive axons may be an important component of amitriptyline''s therapeutic effect in the treatment of neuropathic pain.     

Plasma total homocysteine （THCY） level and other biochemical risk factors in hypertensives with and without cardiovascular events

Objective： The aim of this study is to assess the correlation between traditional cardiovascular risk factors and elevated plasma tHcy level in Nigerian hypertensive. Methods： Thirty-six hypertensive patients were recruited with 36 age and sex-matched controls. The age, sex and anthropometric measurements including height, weight and body mass index （BMI） were taken. Plasma total cholesterol, low density lipoprotein cholesterol （LDL-C）, high density lipoprotein cholesterol （HDL-C）, triglycerides and tHcy were analyzed. The results of the two groups were compared. Results： The mean total cholesterol and LDL- C were significantly higher in the subjects than in the controls （P = 0.01 and 0.03 respectively）. On the other hand, means of HDL-C and triglycerides were not significantly different between the two groups （P =0.06 and 0.68 respectively）. Mean total plasma tHcy was （ 12.95 ±4.9） μmol/L in hypertensive patients when compared with （ 11.29 ±3.6） μmol/L in the controls （P = 0.09） , however the mean tHcy was significantly higher in hypertensive patients who had stroke or myocardial infarction than those without these complications （one way Anova F = 3.63, P = 0.04）. Significant positive correlation was seen between tHcy and systolic blood pressure, diastolic blood pressure, BMI and LDL-C. Conclusion ： The study suggests that elevated plasma tHcy may predict occurrence of cardiovascular complications in hypertensive individuals.     

PLUNC protein expression in major salivary glands of HIV‐infected patients

Oral Diseases (2011) 17 , 258–264 Objective: To analyse and compare the expression of Palate, Lung, and Nasal Epithelium Clone (PLUNC) proteins in salivary glands from patients with and without AIDS (control group) using autopsy material. Methods: We analysed the expression of PLUNCs using immunohistochemistry in parotid (n = 45), submandibular (n = 47) and sublingual gland (n = 37) samples of AIDS patients [30 with normal histology, 21 with mycobacteriosis, 14 with cytomegalovirus (CMV) infection, 30 with chronic non‐specific sialadenitis, and 30 HIV‐negative controls. In situ hybridization (ISH) for SPLUNC 2 in the HIV‐negative group was performed. Results: SPLUNC 1 expression was detected in the mucous acini of submandibular and sublingual glands, and SPLUNC 2 were seen in the serous cells. LPLUNC 1 expression was only positive in the salivary ducts. There was a higher expression of SPLUNC 2 in AIDS patients with CMV infection and mycobacteriosis when compared with all other groups. The intensity of staining for SPLUNC 2 was greater around the lesions than the peripheral ones. ISH for SPLUNC 2 showed perinuclear positivity in the serous cells in all HIV‐negative cases. Conclusions: SPLUNC 1 and LPLUNC 1 proteins were similarly expressed in the salivary glands of AIDS patients and non‐HIV patients. CMV infection and mycobacteriosis increase SPLUNC 2 expression in serous cells in the salivary gland of AIDS patients.     

Intracervical versus vaginal misoprostol for cervical dilatation prior to operative hysteroscopy—a comparative study

Background

Hysteroscopic surgery requires pre-operative cervical ripening to facilitate adequate dilatation of the cervix for insertion of operative hysteroscope. This study was conducted to compare the efficacy of intracervical misoprostol with vaginal misoprostol in achieving cervical ripening before operative hysteroscopy.

Methods

In this randomised comparative study conducted at a tertiary care teaching hospital, 56 patients needing operative hysteroscopy were divided into two groups of 28 patients, one for intracervical misoprostol and the other for vaginal misoprostol. Four hundred microgram of misoprostol was inserted on the night before and in the morning of operative hysteroscopy intracervically in group I and vaginally in group II.

Results

Primary outcome measure was number of patients achieving 7 mm preoperative dilatation of cervix. Largest Hegar dilator that could be passed into the uterine cavity past the internal optic sheath without resistance was noted in each case. Mean cervical dilatation prior to operative hysteroscopy was calculated. In addition, incidence of slipping of vulsellum and cervical laceration was also noted. Time to achieve full cervical dilatation was recorded. In 23/28 cases of group I and 5/28 in group II, size 7 Hegar dilator could be passed without effort. Mean cervical dilatation was 7.5 mm in group I and 5.7 mm in group II. Slipping of the vulsellum and cervical lacerations were seen in significantly less patients in group I. Mean time to achieve cervical dilatation to 10 mm was 43.39 seconds in group I and 103.96 seconds in group II (P<0.0001).

Conclusion

Intracervical administration of misoprostol is an effective method of achieving cervical ripening for easy cervical dilatation up to 10 mm prior to operative hysteroscopy.Key Words: cervical ripening, intracervical administration, misoprostol, operative hysteroscopy     

Trends and cyclic variation in the incidence of childhood type 1 diabetes in two Italian regions over 33 years and during the COVID-19 pandemic

Aim

There is conflicting evidence about the impact of the COVID-19 pandemic on the incidence of type 1 diabetes. Here, we analysed long-term trends in the incidence of type 1 diabetes in Italian children and adolescents from 1989 to 2019 and compared the incidence observed during the COVID-19 pandemic with that estimated from long-term data.

Materials and Methods

This was a population-based incidence study using longitudinal data from two diabetes registries in mainland Italy. Trends in the incidence of type 1 diabetes from 1 January 1989 to 31 December 2019 were estimated using Poisson and segmented regression models.

Results

There was a significant increasing trend in the incidence of type 1 diabetes of 3.6% per year [95% confidence interval (CI): 2.4-4.8] between 1989 and 2003, a breakpoint in 2003, and then a constant incidence until 2019 (0.5%, 95% CI: -1.3 to 2.4). There was a significant 4-year cycle in incidence over the entire study period. The rate observed in 2021 (26.7, 95% CI: 23.0-30.9) was significantly higher than expected (19.5, 95% CI: 17.6-21.4; p = .010).

Conclusion

Long-term incidence analysis showed an unexpected increase in new cases of type 1 diabetes in 2021. The incidence of type 1 diabetes now needs continuous monitoring using population registries to understand better the impact of COVID-19 on new-onset type 1 diabetes in children.