[Application of remote "Internet+" interactive mode in the management of patients with hypertension during normalized epidemic prevention and control of COVID-19].

Objective: To explore the effect of remote "Internet+" interactive management strategy on blood pressure control in patients with hypertension during normalized epidemic prevention and control of COVID-19. Methods: This is a randomized controlled study. A total of 394 patients with hypertension who were treated in Chinese People's Liberation Army General Hospital from October 2019 to December 2020 were randomly divided into experimental group (197 cases) and control group (197 cases). The experimental group adopted remote "Internet+" interaction mode to carry out remote blood pressure intervention, and the control group received traditional blood pressure control mode, and the intervention time was 6 months. Evaluation indicators included blood pressure level, blood pressure lowering speed, time to target blood pressure, blood pressure measurement times, communication times with doctors, medication compliance, blood pressure measurement compliance and disease awareness after 6 months of intervention. The evaluation indexes of the two groups were compared, and the bivariate Pearson correlation analysis was used to explore the relationship between the speed of blood pressure reduction and the times of blood pressure measurement and doctor communication in all patients. Results: A total of 394 patients with hypertension were included in this study, including 209 males, aged (67.6±2.8) years old. After 6 months of intervention, the systolic and diastolic blood pressure of the two groups were both lower than the baseline blood pressure before intervention (both P<0.05), the systolic blood pressure ((125.7±11.7) mmHg (1 mmHg=0.133 kPa) vs. (132.6±12.9) mmHg, P<0.001) and diastolic blood pressure ((72.4±10.7) mmHg vs. (79.8±11.6) mmHg, P<0.001) in the experimental group were lower than those in the control group. The blood pressure reduction speed of the experimental group was faster than that of the control group ((18.63±1.59) mmHg/d vs. (13.26±2.85) mmHg/d, P<0.001), and the time to reach the target blood pressure in the experimental group was shorter than that in the control group ((23.69±2.93) d vs. (47.12±5.81) d, P<0.001). Compared with the control group, the blood pressure measurement times ((0.98±0.13) times/d vs. (0.20±0.40) times/d, P<0.05) and the number of communications with doctors ((0.97±0.16) times/week vs. (0.12±0.32) times/week, P<0.05) were significantly higher in the experimental group. Correlation analysis showed that the speed of blood pressure reduction was positively correlated with the number of blood pressure measurements (r=0.419, P<0.01) and the number of communications with doctors (r=0.857, P<0.01). The proportion of standardized medication (93.91% (185/197) vs. 51.78% (102/197), P<0.001), timely measurement (97.46% (192/197) vs. 47.21% (93/197), P<0.001) and high-degree disease awareness (94.42% (186/197) vs. 49.24% (97/197), P<0.001) were significantly higher in the experimental group than those in the control group. Conclusions: The remote "Internet+" interactive management strategy can effectively improve patients' blood pressure control. The doctor-patient interaction can improve medication compliance and measurement compliance of patients, and help shorten the time to reach the target blood pressure.

Enhanced magnetic circular dichroism by subradiant plasmonic mode in symmetric graphene oligomers at low static magnetic fields.

Giant magnetic circular dichroism (MCD) that shows a different response to incident wave with left or right-handed circular polarization under external magnetic field is promising for magneto-optical sensing, revealing symmetry and degeneracy information of electronic states. However, traditional methods and materials that are used to obtain significant MCD involve highly strong external magnetic field. Based on the excitation of subradiant plasmonic mode and Fano resonance in graphene oligomers in the mid-infrared region, we numerically demonstrate that MCD is enhanced three times larger than the previously reported method, based on the resonance of electric dipole plasmonic mode. This giant MCD is attributed to the remarkably different excitation efficiency of subdradiant plasmonic mode due to the interparticle coupling under left or right-handed circular polarization incidence and external magnetic field. Our results offer an effective mechanism to enhance MCD signal at the nanoscale, which facilitates the sensing, spintronic, nanophotonics and other such fields.

Genetic differentiation of Octopus minor (Mollusca, Cephalopoda) off the northern coast of China as revealed by amplified fragment length polymorphisms.

Octopus minor (Sasaki, 1920) is an economically important cephalopod that is found in the northern coastal waters of China. In this study, we investigated genetic differentiation in fishery populations using amplified fragment length polymorphisms (AFLPs). A total of 150 individuals were collected from five locations: Dalian (DL), Yan-tai (YT), Qingdao (QD), Lianyungang (LY), and Zhoushan (ZS), and 243 reproducible bands were amplified using five AFLP primer combinations. The percentage of polymorphic bands ranged from 53.33 to 76.08%. Nei's genetic identity ranged from 0.9139 to 0.9713, and the genetic distance ranged from 0.0291 to 0.0900. A phylogenetic tree was constructed using the unweighted pair group method with arithmetic mean, based on the genetic distance. The DL and YT populations originated from one clade, while the QD, LY, and ZS populations originated from another. The results indicate that the O. minor stock consisted of two genetic populations with an overall significantly analogous FST value (0.1088, P < 0.05). Most of the variance was within populations. These findings will be important for more sustainable octopus fisheries, so that this marine resource can be conserved for its long-term utilization.

Anticancer effects of suberoylanilide hydroxamic acid in esophageal squamous cancer cells in vitro and in vivo.

The effects of suberoylanilide hydroxamic acid (SAHA), a histone deacetylase inhibitor, have not been studied in esophageal squamous cell cancer (ESCC). Cell viability assay; flow cytometry for cell cycle and annexin V apoptosis assays; assays for cell migration, invasion, and adhesion to extracellular matrix (ECM); and immunoblotting and immunofluorescence staining were performed in three ESCC cell lines. Tumor xenograft with semiquantitative immunohistochemistry was used to study the effects of SAHA in vivo. SAHA effectively inhibited growth of ESCC cells with half-inhibitory concentrations (IC50 ) ranging from 2.6 to 6.5 µmol/L. SAHA restored acetylation of histone 3 lysine 9 (H3K9Ac) and histone 4 lysine 12 (H4K12Ac) with an induction of G1 or G2 cell cycle arrest and apoptosis. Expression of cell cycle checkpoint regulatory proteins including cyclin-dependent kinases (CDKs) and cyclins was decreased, whereas expression of cell cycle suppressors, p21, p27, and Rb was increased in ESCC cells after SAHA treatment. SAHA inhibited migration, invasion, and ECM adhesion in ESCC cells with an induction of E-cadherin expression. SAHA significantly inhibited growth of ESCC tumors with increased expression of p21, p27, Rb, and E-cadherin while decreasing expression of CDK4 and cyclin D1 within the murine tumors. In conclusion, SAHA had antigrowth activity against ESCC cells in vitro and in vivo while inhibiting cell migration, cell invasion, and ECM adhesion, suggesting its potential as an epigenetic therapeutic agent for ESCC.

Effects of high-mobility group box 1 on the proliferation and odontoblastic differentiation of human dental pulp cells.

AIM: To investigate the expression of high-mobility group box 1 (HMGB1) in human dental pulp tissues and the effects of HMGB1 on proliferation and odontoblastic differentiation of human dental pulp cells (hDPCs). METHODOLOGY: Immunohistochemical assay, immunofluorescence staining and flow cytometric analysis were used to detect the expression of HMGB1 in the human dental pulp and hDPCs, respectively. The proliferation of hDPCs was examined by CCK-8 after culturing human primary hDPCs in the presence of HMGB1 with different doses. Odontoblastic differentiation of hDPCs was determined using alkaline phosphatase (ALPase) activity assay and mineralized nodule formation. Important mineralization-related genes such as ALP, dental sialophosphoprotein (DSPP) and dental matrix protein-1 (DMP-1) were determined by real-time polymerase chain reaction. Western blot analysis was performed to determine the difference in expressions of DMP-1 and DSP with or without the presence of exogenous HMGB1. Simultaneously, messenger RNA and protein levels of HMGB1 and RAGE were also detected. The protein level of HMGB1 in the supernatants was quantified using ELISA analysis. RESULTS: HMGB1 was found in human dental pulp tissue and in the nuclei of hDPCs. During hDPC odontoblastic differentiation, HMGB1 translocated from the nuclei to the cytoplasm and then secreted out from hDPCs. Exogenous HMGB1 promoted hDPC proliferation and mineralized nodule formation. It up-regulated the activity of ALPase and the mRNA and protein levels of dentine matrix protein-1 (DMP-1), alkaline phosphatase (ALP), dentine sialophosphoprotein (DSPP) and receptor for advance glycation end (RAGE) of hDPCs. CONCLUSION: HMGB1 promoted the proliferation and odontoblastic differentiation of hDPCs.

Neuronal-derived nitric oxide modulates the activity of mouse detrusor smooth muscle.

AIMS: We investigated the roles of neuronal-derived nitric oxide (NO) in the modulation of spontaneous activity of mouse detrusor smooth muscle. METHODS: Detrusor smooth muscle strips were isolated from nNOS gene knock-out (nNOS(-/-) ) mice and their wild type siblings (nNOS(+/+) ). The properties of smooth muscle cells were assessed using intracellular electrophysiology and Ca(2+) imaging by laser-scanning confocal microscopy. The effects of an nNOS inhibitor, 7-nitro indazole (7-NI) on electrically evoked contractility were assessed using nNOS(+/+) mouse detrusor strips. RESULTS: In spontaneously active cells, the frequency of spontaneous action potentials (sAPs) and whole cell Ca(2+) flashes in nNOS(-/-) preparations was lower than that in the nNOS(+/+) preparations. The frequency of sAPs was enhanced by a nitric oxide donor, diethylamine NONOate sodium salt (NONOate; 100 µM), both when used alone and when the cGMP pathway was blocked by 1H-[1,2,4] oxadiazolo [4,3-a] quinoxalin-1-one (ODQ, 10 µM). 7-NI (100 µM) significantly suppressed the electrically evoked contraction of mouse detrusor strips. CONCLUSIONS: We suggest that neuronal-derived NO facilitates the generation of spontaneous activity via a cGMP-independent pathway, and consequently enhances the evoked contraction of detrusor. Dysregulation of nNOS containing nerves may underlie bladder pathologies.

Effects of varicocele upon the expression of apoptosis-related proteins.

Varicocele-associated apoptosis has been recognised as a cause of male infertility. Thus, we assessed the expression of somatic apoptosis-related proteins (the typical protein-dependent apoptosis markers) in ejaculated sperm plasma from both patients with varicocele and normal donors. We evaluated the relationships between certain apoptosis-related proteins and normal semen quality. Semen samples were obtained from 25 patients with varicocele and from 10 normal fertile controls. These samples were compared using computer-assisted semen analysis for motion parameters and manual analysis for morphology, and were also assayed for apoptosis-related protein activation including caspase-3, poly-ACP-ribose polymerase (PARP), the Bcl-2 family (Bcl-2, Bak) and p53 by means of immunoblot analysis. PARP, Bak and p53 were expressed substantially more in the sperm cells of the varicocele group when compared with the normal group (P < 0.05). The expression of caspase-3 and Bcl-2 did not appear to differ between these two study groups. An increased expression of PARP, Bak and p53 for varicocele-afflicted individuals indicated an increased participation by these agents in the regulating of apoptosis in the ejaculated semen from patients with varicocele, suggesting that certain protein-development apoptotic mechanisms might originate in the cytoplasmic droplet or within mitochondria of spermatocytes and then might function within the nucleus of the cell.

[Genotypes and phenotypes of nine Uygur children with osteogenesis imperfecta in Xinjiang].

Objective: To explore the genotypes and phenotypes of osteogenesis imperfecta (OI) in Xinjiang Uygur children. Methods: The history of nine Uygur children with OI who were hospitalized in First Affiliated Hospital of Xinjiang Medical University from January 2013 to December 2017 were retrospectively reviewed. They were classified into 4 types according to the classical Sillence classification. The genes associated with OI were detected, and the pathogenic variation was assessed by InterVar and Alamut software according to the American College of Medical Genetics and Genomics (ACMG) recommendations. The phenotypes of children with different genotypes were further analyzed. Results: Nine cases aged 3 years and 6 monthes to 15 years were all clinically diagnosed as OI, the clinical manifes tations were repeated fractures, skeletal deformities,short stature, blue sclera, abnormol hearing, hypoplasia of dentin, and relaxation of Joint ligaments, among whom 6 was type Ⅲ OI, 3 were type Ⅳ OI. Nine mutations in 3 genes (COL1A1, COL1A2, and SERPINF1) were detected, and 5 of them were first reported and were all pathogenic variations. Conclusions: The cinical phenotypes of osteogenesis imperfecta in Xinjiang Uygur are complex and varied, but all of them have fractures and skeletal deformities. Genotype is different from that reported at China and abroad, and the SERPINF1 gene may have a higher incidence in Uyghur population. The genetic heterogeneity and unique gene variation pedigree of Uyghur osteogenesis imperfecta defects further provide a basis for the correlation between genotype and phenotype of osteogenesis defects.

Mutations in yeast calmodulin cause defects in spindle pole body functions and nuclear integrity.

Yeast calmodulin (CaM) is required for the progression of nuclear division (Ohya, Y. and Y. Anraku. 1989. Curr. Genet. 15:113-120), although the precise mechanism and physiological role of CaM in this process are unclear. In this paper we have characterized the phenotype caused by a temperature-sensitive lethal mutation (cmdl-101) in the yeast CaM. The cmdl-101 mutation expresses a carboxyl-terminal half of the yeast CaM (Met72-Cys147) under the control of an inducible GAL1 promoter. Incubation of the cmdl-101 cells at a nonpermissive temperature causes a severe defect in chromosome segregation. The rate of chromosome loss in the cmdl-101 mutant is higher than wild-type cell even at permissive temperature. The primary visible defect observed by immunofluorescence and electron microscopic analyses is that the organization of spindle microtubules is abnormal in the cmdl-101 cells grown at nonpermissive temperature. Majority of budded cells arrested at the high temperature contain only one spindle pole body (SPB), which forms monopolar spindle, whereas the budded cells of the same strain incubated at permissive temperature all contain two SPBs. Using the freeze-substituted fixation method, we found that the integrity of the nuclear morphology of the cmdl-101 mutant cell is significantly disturbed. The nucleus in wild-type cells is round with smooth contours of nuclear envelope. However, the nuclear envelope in the mutant cells appears to be very flexible and forms irregular projections and invaginations that are never seen in wild-type cells. The deformation of the nuclear becomes much more severe as the incubation at nonpermissive temperature continues. The single SPB frequently localizes on the projections or the invaginations of the nuclear envelope. These observations suggest that CaM is required for the functions of SPB and spindle, and the integrity of nucleus.

Ejaculatory duct obstruction after transurethral resection of the prostate.

Transurethral resection of the prostate is currently the most commonly employed surgical procedure for benign prostatic hyperplasia. Although several complications after the procedure have been well documented, ejaculatory duct obstruction is a rare complication. We describe this unusual complication in a 77-year-old male who presented with severe pain and a feeling of fullness in the lower abdomen and with dry ejaculate on three occasions after undergoing post-transurethral resection of the prostate. The patient's post-ejaculatory urinalysis demonstrated no sperm. Transrectal ultrasonography also showed no dilatation of the bilateral seminal vesicles or ejaculatory ducts. However, ejaculatory duct obstruction was finally diagnosed on vasovesiculography. The patient was successfully treated with transurethral resection of the ejaculatory duct and remained asymptomatic 6 months postoperatively. Although transrectal ultrasonography is currently widely used to evaluate ejaculatory duct obstruction, we suggest that vasovesiculography is still a feasible and useful tool that provides detailed anatomic information for the advanced confirmation of ejaculatory duct obstruction in patients with a high suspicion of ejaculatory duct obstruction who have normal transrectal ultrasonography findings.

Danish Prostatic Symptom Score is not associated with lower urinary tract symptom severity.

OBJECTIVES: Lower urinary tract symptoms (LUTS) are associated with sexual dysfunction; however, these can vary by population. Thus, the prevalence, severity, and predisposing factors for sexual dysfunction in Taiwanese men (> 40 y) who visited a urologic clinic for LUTS was determined. METHODS: During 2005 and 2006, a prospective survey was carried out which included 412 men with LUTS. Demographic data were collected during face-to-face interviews. Sexual dysfunction and LUTS were evaluated using the Danish Prostatic Symptom Score (DAN-PSS) and the International Prostate Symptom Score (IPSS) questionnaire, respectively. RESULTS: Mild, moderate, and severe LUTS were observed in 25.61%, 47.80%, and 26.59% of the patients, respectively. Reduced or absence of erection, reduced or no ejaculation, and pain upon ejaculation were found in 78.29%, 76.59%, and 6.11% of the patients, respectively. However, only 26.9%, 22.1%, and 4.4% of patients with erectile dysfunction (ED), ejaculatory dysfunction, and pain upon ejaculation were bothered by the sexual dysfunction, respectively. Age was significantly associated with ED, ejaculatory dysfunction (EjD), and pain with ejaculation (p < 0.001). The prevalence of sexual dysfunction increased with the severity of LUTS but was not significantly different. Patients with diabetes were 5.96 times more likely to have sexual dysfunction (95% CI = 1.39 to 25.60; p = 0.017). CONCLUSIONS: Over 70% of LUTS patients in this study suffered from sexual dysfunction. Although age and diabetes were associated with sexual dysfunction, LUTS severity was not.

Holmium: yttrium-aluminum-garnet laser endoureterotomy for benign ureteral strictures: a single-centre experience.

PURPOSE: This study aimed to report the results of endoureterotomy for benign ureteral strictures using the holmium: yttrium-aluminum-garnet laser. MATERIAL AND METHODS: Nineteen patients (8 men and 11 women, mean age 51.47 years) underwent holmium: yttrium-aluminum-garnet laser endoureterotomy for benign ureteral strictures (8 proximal, 3 middle, and 8 distal) using semi-rigid ureteroscopy and 360-microm fibre at 1.2 J/pulse and 10 Hz. After completion of the incision, a 7-Fr double-J ureteral stent was left for 6 weeks. Thereafter, the patients were followed-up by ultrasound and/or intravenous urography at 3-6 monthly intervals. RESULTS: Success was defined as the absence of symptoms plus radiographic resolution of obstructions as assessed by diuretic renography and/or intravenous urography. With a mean follow-up of 40.2 months, success was achieved in 10 (52.6%) of the 19 patients. Nine patients developed recurrent strictures and were considered treatment failures. The stricture length and severity of hydronephrosis correlated with successful outcome, but gender, aetiology, side and location of strictures did not predict outcome. CONCLUSIONS: Although endoureterotomy using a holmium : yttrium-aluminum-garnet laser has an equivocal outcome, the procedure is recommended as a safe, less invasive therapeutic option for the initial management of benign ureteral strictures.

[The role of neutrophil in the pathogenesis of chronic rhinosinusitis].

SummaryChronic nasal-sinusitis is a chronic inflammatory disease characterized by persistent inflammation in the nasal and nasal mucosa. The pathogenesis of CRS is extremely complex and there is currently a lack of effective therapy. The reason for inaccurate diagnosis and invalid treatment of CRS is its sophisticated and unclear mechanism. The pathogenesis of CRS from Asian populations is neutrophil infiltration mediated by Th1/Th17 mixture. Consequently, exploring the function of neutrophil in the pathogenesis of CRS plays an important role in clinical diagnosis and treatment for CRS patients in China.

Graft outcomes of living donor renal transplantations in elderly recipients.

BACKGROUND: Despite the ever-lengthening renal transplant waiting lists, without more donors, living donors serve as a treatment option for patients on dialysis. In the past, patients of advanced age were not considered to be candidates for living donor renal transplantation. Therefore, this study sought to analyze whether older age affects the outcome of living donor renal transplantation. METHODS: A total of 527 primary living donor renal transplantations were performed between January 1, 1995 and January 1, 2006. The subjects were divided into 2 subgroups based on patient age at the time of transplantation. The elder group included all recipients at least 60 years vs the control group of younger patients. RESULTS: Significant differences were observed in readmission rate (elder group, 44%; young group, 31.33%; P = .031) and patient survival rate (P < .001). No significant difference was noted in graft survival rate (P = .201), acute rejection rate (elder group, 10.6%; young group, 13.3%; P = .7), serum creatinine level, or length of stay (elder group, 8.51 days; young group, 6.31 days; P = .083). CONCLUSIONS: Our results confirm that elder patients may benefit from living donor renal transplantation.

Association between lower urinary tract symptoms and sexual dysfunction in Taiwanese men.

The study investigated the association between lower urinary tract symptoms (LUTS) and sexual dysfunction in ageing men. It was a cross-sectional study in an unselected consecutive sample of 398 men aged >40 years attending a urology clinic. LUTS and sexual function were assessed by validated symptom scales, including the International Prostate Symptom Score (IPSS) and the International Index of Erectile Function-5 (IIEF-5). Clinically the severity of total and obstructive IPSS showed no significant correlation with age, but irritative IPSS is statistically correlated with age (P < 0.05). The prevalence of moderate to severe ED (IIEF-5 < 12) was significantly associated with LUTS severity (P < 0.05) and the severity of IIEF-5 correlated significantly with age (P < 0.01). A consistent inverse correlation was found between IIEF-5 and IPSS severity across the age groups, with the strongest effect within aged 60 to 69 years (r = -0.286, P < 0.01). The irritative IPSS showed a significant correlation with IIEF-5 severity across all age groups. These results reveal a significant correlation between LUTS and the severity of ED, especially on the irritative domain.

[Risk for metastasis of lymph node between sternocleidomastoid and sternohyoid muscle in papillary thyroid cancer].

Objective: To analyze the risk factors for metastasis of lymph nodes between sternocleidomastoid and sternohyoid muscle (LNSS) in papillary thyroid cancer (PTC). Methods: Papillary thyroid cancer patients with clinically positive lateral lymph node metastasis (cN1) who underwent surgery including LNSS dissection between May 1, 2013 and May 31, 2016 at the Department of Head and Neck Surgery, Fudan University Shanghai Cancer Center were retrospectively studied. Logistic regression analysis was performed to evaluate possible clinicopathological factors related to LNSS metastasis. Results: In 85 patients, 54 patients (63.5%) showed LNSS in their surgical specimen, and 20 patients (23.5%) had pathologically positive LNSS metastasis. Patients with LNSS showed preoperatively higher levels of serum thyroid stimulating hormone (TSH) and thyroid peroxidase antibody (TPO-Ab) compared to patients only with fibrofatty tissues between sternocleidomastoid and sternohyoid muscle (P<0.05), and they also displayed a higher proportion of multifocality in ipsilateral thyroid lobe (P<0.05). Multi-factor analysis indicated that LNSS metastasis was correlated with original tumor size (OR=1.819, 95%CI 1.050-3.850, P=0.002) and Level Ⅳ lymph node metastasis (OR=2.190, 95%CI 1.132-2.334, P=0.005). Furthermore, the number of positive LNSS was tightly correlated to that of level Ⅳ lymph node metastasis(P<0.05). Conclusion: LNSS metastasis is occult but not quite rare in PTC. Patients with extensive lymph node metastasis in Level Ⅳhave a higher risk for metastasis of LNSS.

CXCR7 mediates TGFß1-promoted EMT and tumor-initiating features in lung cancer.

In the tumor microenvironment, chemokine system has a critical role in tumorigenesis and metastasis. The acquisition of stem-like properties by cancer cells is involved in metastasis and drug resistance, which are pivotal problems that result in poor outcomes in patients with lung cancer. Patients with advanced lung cancer present high plasma levels of transforming growth factor-ß1 (TGFß1), which correlate with poor prognostic features. Therefore, TGFß1 may be important in the tumor microenvironment, where chemokines are widely expressed. However, the role of chemokines in TGFß1-induced tumor progression still remains unclear. In our study, TGFß1 upregulated CXC chemokine receptor expression, migration, invasion, epithelial-mesenchymal transition (EMT) and cancer stem cell (CSC) formation in lung adenocarcinoma. We found that CXCR7 was the most upregulated chemokine receptor induced by TGFß1. CXCR7 knockdown resulted in reduction of migration, invasion and EMT induced by TGFß1, whereas CXCR4 knockdown did not reverse TGFß1-promoted EMT. CXCR7 silencing significantly decreased cancer sphere-forming capacity, stem-like properties, chemoresistance and TGFß1-induced CSC tumor initiation in vivo. In clinical samples, high TGFß1 and CXCR7 expression was significantly associated with the late stages of lung adenocarcinoma. Moreover, TGFß1 and CXCR7 coexpression was positively correlated with the CSC marker, CD44, which is associated with lymph node metastasis. Besides, patients with high expression of both CXCR7 and TGFß1 presented a significantly worse survival rate. These results suggest that the TGFß1-CXCR7 axis may be a prognostic marker and may provide novel targets for combinational therapies to be used in the treatment of advanced lung cancer in the future.

Calbindin d28k overexpression protects striatal neurons from transient focal cerebral ischemia.

BACKGROUND AND PURPOSE: Increased intracellular calcium accumulation is known to potentiate ischemic injury. Whether endogenous calcium-binding proteins can attenuate this injury has not been clearly established, and existing data are conflicting. Calbindin D28K (CaBP) is one such intracellular calcium buffer. We investigated whether CaBP overexpression is neuroprotective against transient focal cerebral ischemia. METHODS: Bipromoter, replication-incompetent herpes simplex virus vectors that encoded the genes for cabp and, as a reporter gene, lacZ were used. Sprague-Dawley rats received bilateral striatal injections of viral vector 12 to 15 hours before ischemia onset. With the use of an intraluminal occluding suture, animals were subjected to 1 hour of middle cerebral artery occlusion followed by 47 hours of reperfusion. Brains were harvested and stained with X-gal (to visualize beta-galactosidase, the gene product of lacZ). The number of remaining virally transfected, X-gal-stained neurons in both the ischemic and contralateral striata were counted and expressed as the percentage of surviving neurons in the ischemic striatum relative to the contralateral nonischemic striatum. RESULTS: Striatal neuron survivorship among cabp-injected animals was 53.5+/-4.1% (n=10) versus 26.8+/-5.4% among those receiving lacZ (n=9) (mean+/-SEM; P<0.001). CONCLUSIONS: We conclude that viral vector-mediated overexpression of CaBP leads to neuroprotection in this model of central nervous system injury. This is the first demonstration that CaBP overexpression protects neurons in a focal stroke model.

Overexpression of the glucose transporter gene with a herpes simplex viral vector protects striatal neurons against stroke.

Herpes simplex virus vectors bearing a glucose transporter (GT) gene and a marker gene were found to protect neurons against a 1-h focal ischemic insult. Rats receiving the GT vector v alpha22beta gal alpha4GT exhibited a 67.4 +/- 35.3% survival of virally targeted neurons in the ischemic hemisphere compared with the contralateral control (n = 7), whereas rats receiving a control vector exhibited only 32.8 +/- 17.9% survival (n = 9). This significant improvement in survival (105%, p=0.022) suggests that energy failure is an important contributor to the neuropathology of ischemic damage in the striatum, and that it can be alleviated by gene transfer. This is the first demonstration of protection against ischemic cerebral injury by the direct transfer of GT genes to neurons.