Comparison of target innervation by sympathetic axons in adult wild type and heterozygous mice for nerve growth factor or its receptor trkA

Nerve growth factor (NGF), a neurotrophin required for the survival and maintenance of postganglionic sympathetic neurons, mediates its trophic effects by activation of its high-affinity receptor trkA. Null mutant mice lacking either NGF or trkA have profound sympathetic deficits, thus revealing the vital importance of NGF synthesis in target tissues and trkA expression by sympathetic neurons. In this study, we sought to assess whether sympathetic neurons of the superior cervical ganglion (SCG) display alterations in their neurochemical phenotype in adult mice carrying one mutated allele for either NGF or trkA, and whether such differences result in altered patterns of innervation to the submandibular salivary gland and pineal gland. In comparison with adult siblings, levels of trkA protein in the SCG were reduced in age-matched NGF(+/-) and trkA(+/-) mice. While NGF(+/-) mice also had significantly fewer sympathetic axons innervating both the submandibular salivary gland and pineal gland, densities of sympathetic axons in both tissues reached normal levels in trkA(+/-) mice. These findings reveal that while levels of trkA are reduced in SCG neurons of adult NGF(+/-) and trkA(+/-) mice (compared with their wild type counterparts), sympathetic axons are capable of achieving normal patterns of target innervation in trkA(+/-) mice but not in NGF(+/-) mice. As NGF protein levels are not depleted in the submandibular salivary gland and pineal gland of NGF(+/-) mice, a loss of sympathetic neurons [Nat Neurosci 1999; 2:699-705], in combination with reduced levels of trkA protein, may account for perturbed patterns of sympathetic innervation to peripheral tissues.     

Effects of the salivary gland massage program in older type 2 diabetes patients on the salivary flow rate,xerostomia, swallowing and oral hygiene: A randomized controlled trial

Aim

To evaluate the effect of a salivary gland massage program to improve salivary flow, swallowing, and oral hygiene in older type 2 diabetes patients.

Methods

This randomized control trial consisted of 73 older diabetes patients with a low salivary flow; 39 and 34 in intervention and control groups, respectively. The intervention group received a salivary gland massage from a trained dental nurse, whereas the control group received a dental education. The salivary flow rates were collected using spit methods at baseline, 1-month and 3-month follow up. All participants were examined for the objective and subjective symptoms of xerostomia, the Simplified Debris Index and the Repetitive Saliva Swallowing Test.

Results

After 3 months, the resting (0.32 vs 0.14 mL/min, P < 0.001) and stimulating salivary flow (3.66 vs 2.83 mL/min, P = 0.025) in the intervention group was significantly higher than the control group. The objective symptoms in the intervention group were significantly lower than the control group after 3 months (1.41 vs 2.26, P = 0.001). The participants who were able to swallow least three times in the Repetitive Saliva Swallowing Test in the intervention group increased by 35.89% after 3 months, whereas the control group increased by 8.82%. Oral hygiene was improved in both groups, but the changes in the intervention were significantly greater than in the control group.

Conclusions

The 3-month salivary glands massage program increases the salivary flow rate, and affects swallowing, objective dry mouth symptoms and oral hygiene in older patients with type 2 diabetes. Geriatr Gerontol Int 2023; 23: 549–557 .     

唇腺活检对诊断干燥综合征的意义

对１９６例可疑的干燥综合征（ＳＳ），患者作了唇腺活检（ＬＳＧ－Ｂ）和Ｓｃｈｉｒｍｅｒ试验、角膜荧光染色和ＳＳ－Ａ／ｓＳ－Ｂ抗体等免疫学检查。１９６例中１１７例ＬＳＧ－Ｂ≥２个灶／４ｍｍ￣２，其中９２例同时有干燥性角膜结膜炎（ＫＣＳ），符合Ｔａｌａｌ的ＳＳ诊断标准。余２５例ＬＳＧ－Ｂ阳性而不伴有ＫＣＳ者，１６例符合继发性ＳＳ（２°ＳＳ），９例有ＳＳ的临床特征表现和ＳＳ一Ａ／ＳＳ－Ｂ阳性而不能排除ＳＳ。此外ＬＳＧ－Ｂ（－）而有ＫＣＳ阳性者１１例均符合原发性ＳＳ（１°ＳＳ）或２°ＳＳ。本组１２８例ＳＳ中ＬＳＧ－Ｂ的阳性率为９１％。我们还发现２°ＳＳ在ＬＳＧ－Ｂ中的灶性涎腺炎严重程度明显轻于１°ＳＳ，而在１°ＳＳ中灶性涎腺炎的严重程度与系统累及呈正相关。     

Impact of gender on insulin signaling pathway in lacrimal and salivary glands of rats

The structure and function of lacrimal and salivary glands present gender differences. Previous works have indicated a synergic action between insulin and androgens over lacrimal gland, and insulin-signaling pathways were recently described in lacrimal gland and salivary gland. Our present study investigates whether gender modulates the early steps of the insulin-signaling system in vivo. Eight-week-old male and female Wistar rats (n=8/group) were compared to evaluate insulin serum levels and insulin tolerance tests by radio-immunoassay and glucose oxidase method, respectively. To assess insulin receptor (IR), Shc, STAT-1, ERK, and Akt phosphorylation in response to insulin in lacrimal gland and salivary gland, tissues from female and male rats (n=5–8/group) were submitted to immunoprecipitation and immunoblotting or Western blotting protocol, and phosphorylation level was determined by densitometry. No difference was found in insulin serum levels or insulin tolerance tests comparing both groups. Nevertheless, lacrimal gland and salivary gland of female rats had a significantly lower insulin-induced IR phosphorylation compared with males. IR phosphorylation was not affected by the estrous cycle stage in either tissue. In addition, in females an apparent but not significant lower STAT and Akt phosphorylation in response to insulin was observed in the lacrimal gland, compared with males. Our findings suggest that alterations in insulin signal transduction may play a role in lacrimal gland and salivary gland gender differences.     

In vitro effects of juvenile hormone on puffing in Chironomys salivary glands

Isolated salivary glands of Chironomus tentons prepupae were incubated in a synthetic culture medium containing 10^?4 M β-ecdysone and various amounts of C18-Cecropia juvenile hormone (JH). After 2 or 4 h their chromosomal puffing patterns were analyzed. Between 3.4 × 10^?7 and 3.4 × 10^?5 M, JH induces the ‘juvenile’ puff I-19-A₁. At higher concentrations (3.4 × 10^?4 M), a previous induction of this puff is reversed. The ecdysone-dependent puff I-18-C becomes progressively reduced at JH concentrations above 3.4 × 10^?6 M. Wounding of glands results in a transient, JH-independent induction and reduction, respectively, of puffs I-19-A₁ and I-18-C, and eventually, in the formation of a new puff (I-19-A₂); wounding generally diminishes the effects of JH on puffing. In the absence of ecdysone, puffs I-19-A₁ and I-19-A₂ develop spontaneously, and 3.4 × 10^?4 M JH no longer reverses puff formation in I-19-A₁. These results suggest an antagonistic interaction of JH and ecdysone with a cellular regulatory circuit involving cell membrane permeability changes.     

Horizontal transmission of de novo hepatitis B between spouses: A case report

We report a female patient with acute hepatitis B due to horizontal transmission of hepatitis B virus from her husband, who suffered from de novo hepatitis B. A 48‐year‐old man underwent peripheral blood stem cell transplantation (PBSCT) for adult T‐cell leukemia/lymphoma. Nine months after the initial treatment, he was referred to our hospital because of jaundice. Laboratory data showed elevated serum aminotransferase levels and hepatitis B surface antigen (HBsAg) positivity. We diagnosed de novo hepatitis B because a pre‐PBSCT serum sample was negative for HBsAg and positive for anti‐hepatitis B core antibody (HBcAb). His liver function improved with entecavir therapy. Two months after his diagnosis of hepatitis B, his 31‐year‐old wife was admitted with fever and appetite loss. She was diagnosed with acute hepatitis B because of increased serum aminotransferase levels and HBsAg and immunoglobulin M HBcAb positivity. Sequencing of HBV DNA in the serum obtained from both patients showed 99.9% homology. Therefore, we diagnosed her acute hepatitis B as due to horizontal transmission of de novo hepatitis B from her husband. HBV derived from de novo hepatitis B should be considered a potential source of infection, although intrafamilial transmission of de novo hepatitis B is rare.     

干燥综合征患者唇腺组织免疫组化特征

目的观察干燥综合征患者的唇腺病理改变及疾病活动和免疫指标的变化。方法取9例干燥综合征患者唇腺组织进行活检,并进行免疫组化染色,同时收集患者的相关临床检验指标。结果免疫组化结果显示：（1）6例患者唇腺组织切片以B细胞浸润为主、2例T／B淋巴细胞为1：1,仅1例以T细胞为主;（2）4例患者唇腺组织切片以CD4＋T为主、2例CIM＋T／CD8＋T为1：1、3例以CD8＋T为主;（3）7例患者唇腺组织切片T细胞内抗原1（T cell intracelluar antigen 1,TIA-1）阳性,6例穿孔素（perforin）阴性;8例Ki-67（＋）淋巴细胞均〈5％;3例AE1／AE3和上皮膜抗原（＋）。实验室检查结果显示：8例干燥综合征患者IgG为（19．54±7．16）g／L;9例类风湿因子为（168±150．93）IU／ml,C-反应蛋白（9．29±11．17）mg／L,血沉（43．56±30．34）mm／h;8例抗核抗体（ANA）阳性,7例抗SS—A抗体阳性,1例抗SS—B抗体阳性。结论T、B淋巴细胞在干燥综合征的发病中具有重要作用。     

Circadian secretion patterns of melatonin after major surgery

Abstract: Biorhythms, such as regular variation in core body temperature and the pattern of the secretion of melatonin, are thought to be mediated by the same biological clock. Core body temperature is affected by the inflammatory response to major surgery. Apart from the well-known inhibitory effect of bright light on its secretion, melatonin is an exceedingly good marker of one of the central generating systems of circadian rhythms. We sequentially measured the plasma melatonin concentration pattern in patients who had undergone esophagectomy with thoracotomy to elucidate the circadian rhythm after major surgery. From seven patients who had received esophagectomy with thoracotomy for esophageal cancer, plasma concentrations of melatonin were measured using an RIA method. Blood samples were collected via each patient's arterial line at 00.00, 02.00, 04.00, 06.00, 08.00, 12.00, 16.00, 20.00, and 24.00 hr on the first postoperative day for six of the patients, and, for one patient, every 2 hr until the third postoperative day and every 4 hr thereafter until the sixth postoperative day. Four patients out of seven had melatonin concentrations of over 30 pg/ml (mean 34 pg/ml) at 24.00 hr on the first postoperative day. Five patients showed circadian secretion patterns of melatonin during the first postoperative day. One patient whose melatonin concentrations were measured consecutively for 6 days showed a regular circadian secretion pattern through the 6 days of the study. Even the stress caused by extremely invasive surgery did not significantly disturb the melatonin secretion pattern.     

The diagnostic utility of labial salivary gland biopsy in IgG4-related disease

Objective: For the definitive diagnosis of IgG4-related disease (IgG4-RD), biopsies of local lesions are recommended so as to exclude other diseases, including lymphoma and cancer. However, performing biopsies of underlying organs is technically difficult. In this study, we examined the diagnostic utility of labial salivary gland (LSG) biopsy as a less invasive procedure.

Methods: Sixty-six patients with suspected IgG4-RD by clinical findings or high serum IgG4 underwent LSG biopsy. We examined the relationship between the number of IgG4-positive plasma cells in LSG and clinical findings.

Results: The final diagnosis was 45 patients with IgG4-RD, 12 with Sjögren’s syndrome, four with suspected Sjögren’s syndrome, three with malignant lymphoma, one with systemic lupus erythematosus, and one with Warthin’s tumor. The sensitivity, specificity, and accuracy of LSG biopsy were 55.6%, 100.0%, and 70.0%, respectively. Forty-five IgG4-RD patients were divided into two groups: 1) 25 with lesions of salivary glands (IgG4-RD S+) and 2) 20 without these lesions (IgG4-RD S?). Seventeen of 25 (68.0%) IgG4-RD S?+?and 8 of 20 (40.0%) IgG4-RD S???patients were positive for LSG biopsy. In the IgG4-RD S???patients, the mean number of affected organs and serum IgG4 in the positive cases for LSG biopsy were significantly higher than in the negative cases.

Conclusion: A solo LSG biopsy is insufficient for the diagnosis of IgG4-RD because of its low sensitivity. However, LSG biopsy combined with clinical findings, including serum IgG4 and number of affected organs, may contribute towards a diagnosis of IgG4-RD patients with affected underlying organs.     

Identification of the active region responsible for the anti-thrombotic activity of anopheline anti-platelet protein from a malaria vector mosquito

We previously identified an anti-platelet protein, anopheline anti-platelet protein (AAPP), from the salivary gland of female Anopheles stephensi (a mosquito vector of human malaria). AAPP specifically blocks platelet adhesion to collagen by binding directly to collagen and subsequently causing platelet aggregation. The aim of this study was to identify the active region of AAPP responsible for the anti-thrombotic activity because we hypothesized that AAPP could be used as a candidate anti-platelet drug. Various truncated forms of AAPP were produced using an Escherichia coli expression system. Each protein was examined for binding activities to soluble/fibrillar collagen and anti-thrombotic activity using a plate assay and platelet/whole blood aggregation study, respectively. Among the truncated forms examined, only a protein encoded by exon 3–4 (rAAPPex_3–4) effectively bound to soluble/fibrillar collagen in a concentration-dependent and saturable manner. The EC₅₀ values of full-length AAPP and rAAPPex_3–4 for soluble collagen binding were 35?nM and 36?nM, respectively. In contrast to soluble collagen, there was a difference in binding affinity to fibrillar collagen between full-length AAPP and rAAPPex_3–4, with EC₅₀ values of 31?nM and 51?nM, respectively. rAAPPex_3–4 also inhibited aggregation of platelets/whole blood, and the IC₅₀ values of full-length AAPP and rAAPPex_3–4 for platelet aggregation were 35?nM and 93?nM, respectively. These results indicated that the essential moiety of AAPP for collagen binding and anti-thrombotic activity was in the region encoded by exon 3–4, which is highly conserved among the counterpart regions of other mosquito species.     

Intra-sellar Salivary Gland-like Pleomorphic Adenoma Arising within Wall of a Rathke's Cleft Cyst

Salivary gland rests occur in the posterior lobe of the pituitary gland near or often communicating with the Rathke's cleft or its cystic subdivisions, and are usually incidental autopsy findings. They are attributed to the oropharyngeal development of the Rathke's pouch and may rarely give rise to salivary gland-like tumors in the sella. We present a pleomorphic adenoma, a rare tumor of the sellar region, that has not been previously recognized in association with Rathke's cleft cyst. It occurred in a 44-year-old man who presented with hypopituitarism and reduced vision. Magnetic resonance imaging showed a sellar mass with suprasellar extension which was totally removed. It consisted of segments of a cyst wall lined by focally ciliated columnar of cuboid epithelium containing goblet cells. An eosinophilic granular material with cholesterol clefts represented the contents of the cyst. Within its wall there was a tumor with ductal structures and non-ductal varied cellular components including hypercellular areas of spindle and ovoid cells forming interlacing fascicles. Individual cells appeared to float in abundant mucinous material. The appearances were those of a salivary gland pleomorphic adenoma arising within the wall of a Rathke's cleft cyst. The myoepithelial nature of non-ductal tumor cells was confirmed with immunocytochemistry. The existence of seromucous glands communicating with the Rathke's cleft remnants, explains the concomitant occurrence of the tumor and the cyst. This rare neoplasm from salivary gland rest should be considered in the differential diagnosis of unusual sellar and suprasellar tumors.     

Transmission of enteric non-A, non-B hepatitis virus in Macaca mulatta, monkeys by intraportal route: Subsequent passages of HEV virus

Macaca mulatta monkeys have been used for the transmission of enteric non-A, non-B hepatitis (HEV) virus by intraportal route. Subsequent passages of HEV virus have been completed in these monkeys. In the first passage, 2 monkeys were inoculated by intra-portal route with 27-34 nm virus-like particles (VLP) obtained from known epidemics of HEV hepatitis in India, and biochemical and serological changes in the blood, histological changes in the liver and excretion of 27-34 nm VLP in the stool were studied. Results were compared with those of 4 negative control monkeys inoculated with stool extracts from healthy individuals. The second passage of 27-34 nm VLP was carried out on 2 monkeys using pools of stool suspension positive for 27-34 nm VLP from first passaged animals. Similarly, the third passage of 27-34 nm VLP was completed intraportally in another monkey. All monkeys developed acute hepatitis, as evidenced by transient elevation of aminotransferase, histopathological changes in the liver, development of antibodies aggregating 27-34 nm VLP and excretion of 27-34 nm VLP in stools. No control monkeys developed these features.     

2014年美国胃肠病学会指南:免疫抑制剂治疗过程中HBV再激活的预防及治疗

<正>本指南旨在转述美国胃肠病学会(AGA)关于免疫抑制应用患者HBV再激活的预防及治疗策略,由临床实践和质量管理委员会(美国临床实践指南委员会)编制,并得到AGA理事会授权。本指南是由AGA参考一份已发表指南的相关流程制订的[1]。简而言之,本指南中包括了对推荐等级的评估、制订与评价方法(GRADE)[2]以及医学研究机构的最佳临床实践[3]。按照GRADE方法的要求,准备及收集指南相关的文献资料,