Modulation of protective immunity against herpes simplex virus via mucosal genetic co-transfer of DNA vaccine with beta2-adrenergic agonist

Cholera toxin, which has been frequently used as mucosal adjuvant, leads to an irreversible activation of adenylyl cyclase, thereby accumulating cAMP in target cells. Here, it was assumed that beta2-adrenergic agonist salbutamol may have modulatory functions of immunity induced by DNA vaccine, since beta2-adrenergic agonists induce a temporary cAMP accumulation. To test this assumption, the present study evaluated the modulatory functions of salbutamol co-administered with DNA vaccine expressing gB of herpes simplex virus (HSV) via intranasal (i.n.) route. We found that the i.n. co-administration of salbutamol enhanced gB-specific IgG and IgA responses in both systemic and mucosal tissues, but optimal dosages of co-administered salbutamol were required to induce maximal immune responses. Moreover, the mucosal co-delivery of salbutamol with HSV DNA vaccine induced Th2-biased immunity against HSV antigen, as evidenced by IgG isotypes and Th1/Th2-type cytokine production. The enhanced immune responses caused by co-administration of salbutamol provided effective and rapid responses to HSV mucosal challenge, thereby conferring prolonged survival and reduced inflammation against viral infection. Therefore, these results suggest that salbutamol may be an attractive adjuvant for mucosal genetic transfer of DNA vaccine.

Behavioral Manifestation of Neuropathic Pain Following Sciatic Nerve Section in Rats

The present study was performed to observe the time course of behavioral signs of painful sensations in sciatic neurectomy animal model and to test the effects of sympathectomy and saphenous nerve section on these behavioral signs. Sciatic nerve was ligated and cut at the mid-thigh level under gaseous anesthesia. The application of von Frey filaments to the medial plantar surface of foot revealed weak and long-lasting mechanical allodynia (until end of test period, 20 weeks PO). Acetone application to the plantar surface of foot was used ti measure the sensitivity to cold stimulation. Cold allodynia which is interpreted as increased response to acetone application developed fairly well and lasted the end of test period (20 weeks PO). The cumulative duration of foot lifts off neutral or cold plate was used to test spontaneous, ongoing pain and was increased until 16 weeks PO and 20 weeks PO respectively. These results suggest that sciatic neurectomy which has been widely used as chronic pain model shows behavioral signs suggsting painful sensations except autotomy, which has been used as index of pain in experimental animal. Surgical sympathectomy performed 1 week after sciatic neurectomy partially reduced the behavioral signs of mechanical allodynia and cold allodynia, suggesting behavioral changes developed following section of sciatic nerve was partially sympathetic dependent. Saphenous nerve section 1 week after sciatic neurectomy almost completely reduced mechanical allodynia and cold allodynia, but did not change spontaneous, ongoing pain. These results suggest that evoked responses such as mechanical and cold allodynia are mediated by saphenous nerve activity and activating and/or maintaining mechanisms of spontanous, ongoing pain and evoked pain may be different.

Polarization of protective immunity induced by replication-incompetent adenovirus expressing glycoproteins of pseudorabies virus

Replication-incompetent adenoviruses expressing three major glycoproteins (gB, gC, and gD) of pseudorabies virus (PrV) were constructed and used to examine the ability of these glycoproteins to induce protective immunity against a lethal challenge. Among three constructs, recombinant adenovirus expressing gB (rAd-gB) was found to induce the most potent immunity biased to Th1-type, as determined by the IgG isotype ratio and the profile of the Th1/Th2 cytokine production. Conversely, the gC-expressing adenovirus (rAd-gC) revealed Th2-type immunity and the gD-expressing adenovirus (rAd-gD) induced lower levels of IFN-gamma and IL-4 production than other constructs, except IL-2 production. Mucosal delivery of rAd-gB induced mucosal IgA and serum IgG responses and biased toward Th2-type immune responses. However, these effects were not observed in response to systemic delivery of rAd-gB. In addition, rAd-gB appeared to induce effective protective immunity against a virulent viral infection, regardless of whether it was administered via the muscular or systemic route. These results suggest that administration of replication-incompetent adenoviruses can induce different types of immunity depending on the expressed antigen and that recombinant adenoviruses expressing gB induced the most potent Th1-biased humoral and cellular immunity and provided effective protection against PrV infection.

Recognition of Family Practitioners on Cold Hands/Feet Syndrome and Raynaud's Disease

BACKGROUND: Many patients with "cold hands/feet syndrome" have been taking herbal medicine or medicine to improve blood circulation without proven evidence. Raynaud's disease had been neglected in primary care. This study was conducted to investigate the recognition for Raynaud's disease and "cold hands/feet syndrome" by family doctors. METHODS: A questionnaire was posted to 905 family doctors who were in practice from January to July 2003. RESULTS: Among the 274 respondents, 58 (21%) reported that they have seen patients with "sensitive to cold" frequently and 208 (76%) doctors have seen such patients sometimes. Only 8 (3%) doctors answered that they have never seen patients with such symptoms. When such patients see a doctor and complain of "cold hands/feet syndrome", most doctors (60%) prescribed medicine that improved blood circulation (83%) or calcium channel blockers (9%). In case of questions like 'Do you suspect "cold hands/feet syndrome" or "sensitive to cold" contain Raynaud's disease?', 132 (48%) doctors answered 'yes'. And among the 132 doctors, only 15 (11.2%) doctors thought that those patients with "cold hands/feet syndrome" had Raynaud's disease. In addition when the doctors diagnosed the condition as Raynaud's disease, 54% prescribed medicine that improved blood circulation (52%) or calcium channel blockers (40%). CONCLUSION: Most doctors prescribe medicine that improves blood circulation for cold hands/feet syndrome. Many doctors also prescribe medicine to improve blood circulation for Raynaud's disease frequently. The result of our study suggests that there is a need to train doctors so that recognized and diagnosed Raynaud's disease can be correctly.

Recognition of Family Practitioners on Cold Hands/Feet Syndrome and Raynaud's Disease

BACKGROUND: Many patients with "cold hands/feet syndrome" have been taking herbal medicine or medicine to improve blood circulation without proven evidence. Raynaud's disease had been neglected in primary care. This study was conducted to investigate the recognition for Raynaud's disease and "cold hands/feet syndrome" by family doctors. METHODS: A questionnaire was posted to 905 family doctors who were in practice from January to July 2003. RESULTS: Among the 274 respondents, 58 (21%) reported that they have seen patients with "sensitive to cold" frequently and 208 (76%) doctors have seen such patients sometimes. Only 8 (3%) doctors answered that they have never seen patients with such symptoms. When such patients see a doctor and complain of "cold hands/feet syndrome", most doctors (60%) prescribed medicine that improved blood circulation (83%) or calcium channel blockers (9%). In case of questions like 'Do you suspect "cold hands/feet syndrome" or "sensitive to cold" contain Raynaud's disease?', 132 (48%) doctors answered 'yes'. And among the 132 doctors, only 15 (11.2%) doctors thought that those patients with "cold hands/feet syndrome" had Raynaud's disease. In addition when the doctors diagnosed the condition as Raynaud's disease, 54% prescribed medicine that improved blood circulation (52%) or calcium channel blockers (40%). CONCLUSION: Most doctors prescribe medicine that improves blood circulation for cold hands/feet syndrome. Many doctors also prescribe medicine to improve blood circulation for Raynaud's disease frequently. The result of our study suggests that there is a need to train doctors so that recognized and diagnosed Raynaud's disease can be correctly.

The Prevelance of Diagnosis as Raynaud's Disease among the People Complaint of Abnormal Sensation on Hands and Feet

BACKGROUND: The previous studies suggested that the rate of the people who reported having sensitivity to cold and Raynaud's disease were 12% and 5~10% of general population respectively. There are surprisingly few data on 'cold hands and feet syndrome', the conventional circulatory disorder in far-eastern Asia in spite of the assumption that it is a common disorder among Korean population. Besides, the prevalence of Raynaud's disease has not been studied for Korean complaint of the syndrome. Therefore, we conducted the survey regarding the frequency of Baynaud's disease and phenomenon among the people appealed abnormal sensory symptoms on hands and feet, and 'cold hands and feet syndrome'. METHODS: The questionnaires were asked to 1,008 out- patients who complained abnormal sensory symptoms on hands and feet. The subjects were screened among the patients who visited the clinics, mainly department of family medicine in Uijongbu St. Mary's hospital from January to July 2003. RESULTS: The most common abnormal sensory symptoms were tingling feeling and coldness, pain in the descending order. The mean age of the patients is 47 years, the average age at the onset of the symptoms is 40 years, and the mean duration they had been suffered by the symptoms is 7 years. During interview, 289 patients voluntarily appealed 'cold hands and feet syndrome' in expression of "I have cold extremities" or "I have the syndrome". Among the screened patients, 510 patients answered, "yes" to the question "Are your fingers unusually sensitive to cold?" Two hundred and nineteen patients (43%) of them showed Raynaud's phenomenon. One hundred and sixty patients were diagnosed as Raynaud's disease among 219 patients who had Raynaud's phenomenon. The rest 59 patients were diagnosed as secondary Raynaud's phenomenon. Eighty-seven patients (30%) of 289 patients who voluntarily reported 'cold hands and feet syndrome' were diagnosed as Raynaud's disease. The average age of Raynaud's disease patients is 37 years old, average first attack age is 24 years, and average suffering period is 14 years. Only 10% of cases experienced the first attacks after 40 years old. The attack rates are different by gender. The ratio is 2.3 and higher in female. Only six patients (4%) of Raynaud's disease had been diagnosed accurately. Fifty-three patients (33%) have family history and 41 of them are the first-degree relatives. The causes of secondary Raynaud's phenomenon (59 patients) are connective tissue disorders, neurologic diseases, carpal tunnel syndrome, hypothyroidism, vascular disorders, etc. The statistically significant factors that influence on Raynaud's disease are female, below 40 years old, stress, family history, hypertension, diabetes, etc. The statistical analysis in this study does not prove the association between the disease and the factors such as physical labor, manual labor using hands heavily, smoking, drinking, thyroid diseases, joint disorders, ischemic heart disease, depression. CONCLUSION: Raynaud's disease has been underlooked even though it is not uncommon and can be easily diagnosed and treated. In conclusion, the result of our study suggests that abnormal sensory symptoms on hands and feet, especially 'cold hands and feet syndrome', the conventional circulatory disorder, are the medical condition where special concern on Raynaud's disease is required.

The Combined Therapeutic Effect of Drugs in Experimental Acute Focal Cerebral Ischemia

The study was designed to examine the effects of pretreatment with mannitol, methyl prednisolone and nimodipine on the acute focal cerebral ischemia in the cats of occlusion of the proximal part of the middle cerebral artery via the postorbital approach. The energy metabolisms of the brain was measured utilizing the high liquid performance chromatography in the brain tissues of cats. The experimental animals were seperated into 3 groups. group I: the sham control group. group II: the recirculation group. group III: the treatment group. There were significant increase in the ATP, GTP, UTP and E.C. levels in focal ischemic cerebral tissues of the treatment group when compared with the recirculation group. It is suggested that pretreatment with the combination of these drugs may prevent the ischemic damage from the acute focal cerebral ischemia by the maintenance of high energy metabolites. However further studies should determine the synergistic pharmacologic mechanisms in this therapeutic strategy.