Donepezil plus estradiol treatment enhances learning and delay-dependent memory performance by young ovariectomized rats with partial loss of septal cholinergic neurons

Effects of estrogen therapy on cognitive performance appear to diminish with age and time following the loss of ovarian function. We hypothesize that this is due to a reduction in basal forebrain cholinergic function and that treatment with a cholinergic enhancer can reverse the effect. This study tested whether combining the cholinesterase inhibitor donepezil with estradiol treatment can enhance/restore estradiol effects on cognitive performance in young ovariectomized rats with selective lesions of septal cholinergic neurons. 192IgG-saporin was injected directly into the medial septum to produce selective cholinergic lesions. Rats were then treated with donepezil (Don, daily injections of 3 mg/kg/day, i.p.) or vehicle, and then with 17β-estradiol (E2, administered by silastic capsule implanted s.c.) or an empty capsule. Rats were trained on a delayed matching-to-position (DMP) T-maze task which previous studies have shown is sensitive to ovariectomy and estrogen replacement. Results show that neither estradiol nor donepezil alone significantly enhanced acquisition of the DMP task in rats with cholinergic lesions. Combination therapy was effective, however, depending on the severity of the lesion. Don + E2 significantly enhanced acquisition of the task in rats with partial lesions (< 50% loss of cholinergic neurons), but not in rats with severe lesions. This effect was due largely to a reduction in perseverative behavior. Don + E2 also improved working memory in rats with partial lesions, as evidenced by significantly better performance than controls during increased intertrial delays. These findings suggest that even partial loss of septal cholinergic neurons can reduce effects of estrogen therapy on cognitive performance, and demonstrate that combining a cholinesterase inhibitor with estrogen therapy can help to restore beneficial effects on performance. We propose that combination therapy may have similar beneficial effects in women, particularly in older women who have not used estrogen therapy for many years and are beginning to show signs of cognitive impairment or early Alzheimer's disease.     

不同术前皮肤准备方案与手术切口感染的关系研究

目的:研究不同术前皮肤准备方案与手术切口感染(SSI)的关系,为降低临床SSI发生率提供参考.方法:选择自2015年1月～2019年12月在医院行手术治疗的患者1810例为本次研究对象.根据析因设计表,将因素A:是否剃毛(1不剃毛;2剃毛),B:清洁方式(1清水清洁;2肥皂水清洁),C:术前备皮时间(1术前ld;2术前...     

医学生实习中外科基本操作常犯错误及对策分析

目的：探讨医学生临床实习中在基本操作上常犯的错误,并对此提出建议和纠正措施,旨在进一步提高临床带教水平及临床教学质量。方法i总结我院临床医学专业实习生进行常见的外科临床基本操作考核成绩的情况,对错误类型等进行统计并提出合理的解决措施。结果：共考察学生90名,其中外科换药方法欠佳者22人（24．4％）,消毒铺巾存在问题24人（26．6％）,缝合存在问题32人（35．5％）,打结存在问题38（42．2％）人,拆线存在问题19（21．1％）人。结论：加强医学生外科实习期间的无菌观念培养及强化手术基本操作是临床教学的重要环节。     

Reaktionsmuster verschiedener Mittel-und Zwischenhirnzentren von Rana temporaria L. nach Unterbrechung der Nervenbahnen des Pinealkomplexes

Zusammenfassung Der Einfluß des lichtempfindlichen Pinealkomplexes (Stirnorgan und Epiphysis cerebri) von Rana temporaria auf dorsale diencephale und mesencephale Hirnzentren breitet sich über ein größeres Gebiet aus als man bisher angenommen hat. Nach operativer Unterbrechung des Nervus- und Tractus pinealis wurde mit Punktzählverfahren die Dichte der Zell- und Zellkernvolumina sowie der Kapillaroberfläche im dorsalen Thalamus, mesencephalen (postthalamischen) zentralen Grau, Ganglion habenulae, Tectum opticum, in der Area praetectalis und im Subcommissuralorgan (Sco) bestimmt. Die morphometrischen Meßergebnisse lassen sich wie folgt interpretieren: 1. Der Pinealkomplex wirkt auf das Sco, das zentrale Grau und die Area praetectalis ein (vgl. Paul u. Mitarb., 1971); das Sco wird in erster Linie über das Stirnorgan beeinflußt. 2. Weitere Kerngebiete des Zwischenhirns (Ganglion habenulae und dorsaler Thalamus) gehören funktionell zu dem vom Pinealkomplex kontrollierten System. 3. Die von Kemali und Braitenberg (1970) beschriebene Asymmetrie der Ganglia habenularum zeigt sich auch im funktionellen Zusammenspiel dieser Kerngebiete mit dem Pinealkomplex, dem dorsalen Thalamus und dem dorsalen Abschnitt des zentralen Graus. Die in Stirnorgan und Epiphysis cerebri transformierten Lichtreize werden in Hirnabschnitte weitergeleitet, die olfaktorische und retinale Signalmuster verarbeiten. Über die biologische Bedeutung der nervösen Beziehungen des Stirnorgans zum sekretorischen Sco können noch keine Angaben gemacht werden.

---

Study of mesencephalic and diencephalic centers after transection of the centripetal nervous pathways of the pineal complex in Rana temporaria L.

Summary Nervous influences of the pineal complex of the frog, Rana temporaria, exerted upon mesencephalic and diencephalic centers were investigated using morphometric methods after the transection of the nervus or the tractus pinealis. Densities of the cell- and nuclear volumes and of the capillaries were measured by a point-counting method in the dorsal thalamus, the mesencephalic (postthalamic) central gray, the habenular ganglion, the optic tectum, the pretectal area, and the subcommissural organ (sco). The morphometric measurements showed: 1. A functional influence of the pineal complex on the sco, the central gray, and the pretectal area (see Paul et al., 1971); the frontal organ seems to be primarily related to the sco. 2. The habenular ganglia and the dorsal thalamus belong to a system which is controlled by the pineal complex. 3. The morphological asymmetry of the habenular ganglia (Kemali and Braitenberg, 1970) has an influence on the functional interactions between the pineal complex, the dorsal thalamus, and the central gray. The impulses arising in the light-sensitive pineal complex of the frog are conducted to brain regions which are known to integrate olfactory and retinal sensory inputs. The functional significance of the nervous connexion of the frontal organ with the secretory sco is still open to discussion.

Mit Unterstützung durch die Deutsche Forschungsgemeinschaft (Arbeitskreis Prof. Dr. A. Oksche).     

Esophageal squamous cell carcinoma and adenocarcinoma in Malaysia – Pooled data from upper gastrointestinal centers in a multiethnic Asian population

BackgroundEsophageal cancer is the sixth leading cause of cancer death worldwide with considerable geographical histological variation There is a paucity of data in esophageal cancer in demographics, histology, and survival among the multi-ethnic Malaysian population. This paper is a review of esophageal cancer epidemiology and survival among esophageal cancer patients from data collected by the Malaysian Upper Gastrointestinal Surgical Society.MethodsThis is a multicenter retrospective observational study of esophageal cancer patients from six upper gastrointestinal surgical centers in Malaysia between 2005 and 2019. Patient characteristics, histological type and stage were compared and survival analyzed.ResultsThere were 820 patients with esophageal cancer included, where 442 (53.9 %) cases had squamous cell carcinoma (SCC) and 378 (46.1 %) had adenocarcinomas (AC). Malays were the predominant ethnicity with AC (66.7 %) while Indians were the ethnic majority (74.6 %) with SCC. Majority of patients (56.8 %) presented as stage IV disease. Overall, the 1-, 3-, and 5-years’ survival were 35.8 %, 13.8 % and 11.0 %, respectively. Surgical resection with curative intent yielded the best 5-year survival (29.4 %). Intervention in stage IV AC yielded superior survival when compared to SCC (median survival, 7.9 months vs 4.8 months; p, 0.018) Our series demonstrated an increase in AC to SCC over the last 15 years.ConclusionsThere was an ethnic preponderance seen between different histology in this region, not previously discussed. An increase in AC was observed over the last 15 years. Late diagnosis seen in most patients imparts poor prognosis as curative surgery affords the best outcome.     

5/6th Nephrectomy in Combination with High Salt Diet and Nitric Oxide Synthase Inhibition to Induce Chronic Kidney Disease in the Lewis Rat

Chronic kidney disease (CKD) is a global problem. Slowing CKD progression is a major health priority. Since CKD is characterized by complex derangements of homeostasis, integrative animal models are necessary to study development and progression of CKD. To study development of CKD and novel therapeutic interventions in CKD, we use the 5/6th nephrectomy ablation model, a well known experimental model of progressive renal disease, resembling several aspects of human CKD. The gross reduction in renal mass causes progressive glomerular and tubulo-interstitial injury, loss of remnant nephrons and development of systemic and glomerular hypertension. It is also associated with progressive intrarenal capillary loss, inflammation and glomerulosclerosis. Risk factors for CKD invariably impact on endothelial function. To mimic this, we combine removal of 5/6th of renal mass with nitric oxide (NO) depletion and a high salt diet. After arrival and acclimatization, animals receive a NO synthase inhibitor (NG-nitro-L-Arginine) (L-NNA) supplemented to drinking water (20 mg/L) for a period of 4 weeks, followed by right sided uninephrectomy. One week later, a subtotal nephrectomy (SNX) is performed on the left side. After SNX, animals are allowed to recover for two days followed by LNNA in drinking water (20 mg/L) for a further period of 4 weeks. A high salt diet (6%), supplemented in ground chow (see time line Figure 1), is continued throughout the experiment. Progression of renal failure is followed over time by measuring plasma urea, systolic blood pressure and proteinuria. By six weeks after SNX, renal failure has developed. Renal function is measured using ''gold standard'' inulin and para-amino hippuric acid (PAH) clearance technology. This model of CKD is characterized by a reduction in glomerular filtration rate (GFR) and effective renal plasma flow (ERPF), hypertension (systolic blood pressure>150 mmHg), proteinuria (> 50 mg/24 hr) and mild uremia (>10 mM). Histological features include tubulo-interstitial damage reflected by inflammation, tubular atrophy and fibrosis and focal glomerulosclerosis leading to massive reduction of healthy glomeruli within the remnant population (<10%). Follow-up until 12 weeks after SNX shows further progression of CKD.     

Surgical issues surrounding use of aromatase inhibitors

There are important surgical issues related to the use of the third generation aromatase inhibitors in both the neoadjuvant and adjuvant settings. Neoadjuvant hormone therapy is effective at downstaging tumours, particularly large tumours initially thought to be inoperable or requiring mastectomy. Randomised trials have shown that the newer aromatase inhibitors letrozole and anastrozole increase the numbers of women who are suitable for breast-conservation compared with tamoxifen, and that letrozole is superior to tamoxifen in terms of clinical response.

Aromatase inhibitors are most effective in ER-rich tumours and are clinically and biologically effective in both HER2 positive and negative tumours, whereas HER2 positive tumours show a level of resistance to tamoxifen.

In neoadjuvant studies comparing aromatase inhibitors with tamoxifen, the duration of use has been 3–4 months, by which time any response is usually evident but longer treatment periods produce continued shrinkage and response. The re-excision rate following breast conservation surgery after neoadjuvant hormone therapy is favourable compared with the rates following immediate wide local excision. Local recurrence rates are acceptable in patients undergoing neoadjuvant therapy and breast-conserving surgery providing post-operative radiotherapy is given.

Adjuvant aromatase inhibitors, as well as having an effect on metastatic disease and survival, reduce local and regional recurrence.     

Collecting And Measuring Wound Exudate Biochemical Mediators In Surgical Wounds

We describe a methodology by which we are able to collect and measure biochemical inflammatory and nociceptive mediators at the surgical wound site. Collecting site-specific biochemical markers is important to understand the relationship between levels in serum and surgical wound, determine any associations between mediator release, pain, analgesic use and other outcomes of interest, and evaluate the effect of systemic and peripheral drug administration on surgical wound biochemistry. This methodology has been applied to healthy women undergoing elective cesarean delivery with spinal anesthesia. We have measured wound exudate and serum mediators at the same time intervals as patient''s pain scores and analgesics consumption for up to 48 hours post-cesarean delivery. Using this methodology we have been able to detect various biochemical mediators including nerve growth factor (NGF), prostaglandin E2 (PG-E2) substance P, IL-1β, IL-2, IL-4, IL-6, IL-7, IL-8, IL-10, IL-12, IL-13, IL-17, TNFα, INFγ, G-CSF, GM-CSF, MCP-1 and MIP-1β. Studies applying this human surgical wound bioassay have found no correlations between wound and serum cytokine concentrations or their time-release profile (J Pain. 2008; 9(7):650-7).¹ We also documented the utility of the technique to identify drug-mediated changes in wound cytokine content (Anesth Analg 2010; 111:1452-9).²     

Excessive increase of serum interleukin 6 jeopardizes host defense against multi-bacterial infection

Serum interleukin 6 (IL-6) is elevated among patients who have undergone surgery, trauma, and thermal injury. It is well known that the greater the increase of serum IL-6, the higher the incidence of post-injury morbidity and mortality is. However, it has not been determined whether the physiological effects of IL-6 increase the rate of morbidity and mortality or if IL-6 is just a bystander that only indicates the severity of the injury. To elucidate this, we planned to investigate the effect of IL-6 on a multi-bacterial infection, one of the most frequent post-injury complications. CDF1 male mice were administered recombinant human IL-6 (hIL-6) continuously at a dose of 0, 1, or 10 microg/day. The mice then underwent cecal ligation without puncture that induced slow multi-bacterial infection. The survival rate of mice receiving 10 microg/day of hIL-6 was significantly lower (38.5%) than the rate of those receiving 0 (83.3%) or 1 (92.3%) microg/day of hIL-6. The result of this study showed that only excessive increases in serum IL-6, to levels that were observed among patients who underwent severe injury or extensive surgery with high incidence of post-injury infection, jeopardize the host's defense against bacterial infection.