A Case of Headache Treated by Online Telemedicine in Collaboration With a Midwifery Home.

Midwifery centers are places where midwives not only provide antenatal checkups and delivery care but also offer a wide range of health guidance to pregnant women, postpartum mothers, newborns, and older women. In recent years, midwives have also provided onsite and online health guidance. However, diagnosis and prescribing medication are impossible in midwifery centers because no doctor is present. If the midwife determines that the patient should consult doctors, the patient may have to go to a hospital and see doctors in person, which can be burdensome. Online telemedicine facilitates midwife-doctor collaboration and may solve this problem. We report a case of headache management by telemedicine that minimized the patient's travel burden by collaborating with a midwifery center that provides onsite, visiting, and online health guidance for patients who have difficulty visiting a hospital due to postpartum period, childcare, and breastfeeding. A 29-year-old woman and her husband were raising an infant in Sado City (a remote island across the sea), Niigata Prefecture. She developed acute back pain and was bedridden for several days due to immobility. She consulted a midwife because of stress and anxiety caused by childcare and acute back pain, as well as newly occurring headaches. The midwife visited her and provided on-site health guidance. The midwife decided that a doctor's diagnosis and treatment with painkillers were desirable for the headache and back pain, so she contacted a doctor based on the patient's request. The doctor provided online telemedicine across the sea, diagnosed her headache as a tension-type headache, and prescribed acetaminophen 500 mg as an abortive prescription. The prescription was faxed to a pharmacy on the island, and the original was sent by post. The midwife picked up the medication and delivered it to the patient. After taking the medication, the patient's back pain and headache went into remission. Collaboration between midwifery centers that provide onsite, visiting, and online health guidance and medical institutions that offer online telemedicine can potentially improve accessibility to medical care. It differs from conventional online telemedicine in the midwife's coordination practice by monitoring the patient's condition and requesting the physician based on the patient's request.

Acute superoxide scavenging restores depressed baroreflex sensitivity in renovascular hypertensive rats.

In some pathological conditions such as hypertension, there is an impairment in the autonomic control of blood pressure resulting in changes in baroreflex sensitivity. In the present study we tested the hypothesis that acute superoxide scavenging would restore the reduced baroreflex sensitivity in renovascular hypertension. Male Wistar rats underwent 2-Kidney-1-Clip (2K1C) or sham surgery and were maintained untouched for six weeks to develop hypertension. After six weeks, animals from the 2K1C group were hypertensive when compared to the sham group (165±9 vs. 108±7mm Hg, P<0.05). As a proof of principle for the hypertension model adopted, animals from the 2K1C group presented increased non-clipped kidney and cardiac mass index and reduced clipped kidney mass index. Regarding baroreflex, 2K1C rats presented diminished baroreflex sensitivity when compared to the sham group (2K1C+saline: -1.61±0.15 vs. sham+saline: -2.79±0.24bpm mm Hg(-1), p<0.05). Moreover, acute administration of Vitamin C (150mg/Kg, i.v.) restored baroreflex sensitivity in 2K1C rats (2K1C+Vit C: -3.08±0.37 vs. 2K1C+saline: -1.61±0.15bpm mm Hg(-1), p<0.05). Furthermore, administration of apocynin (30µg/Kg, i.v.), a NADPH oxidase inhibitor, also improved baroreflex sensitivity in the 2K1C group (2K1C+apocynin: -2.81±0.24 vs. 2K1C+saline: -1.61±0.15bpm mm Hg(-1), p<0.05). In addition, autonomic blockade with either methylatropine or propranolol reduced the changes in heart rate to the same extent in all groups suggesting that improved baroreflex sensitivity by antioxidants were mediated by improvement in autonomic function. Taken together, these data suggest that NADPH oxidase-derived reactive oxygen species are involved in the blunted baroreflex sensitivity in renovascular hypertension and that acute scavenging of superoxide restores baroreflex sensitivity.

Role of mu-calpain in human decidua for recurrent miscarriage.

PROBLEM: Earlier, we showed that calpain activated by increasing intracellular calcium ion concentration in endometrial cells, causes endometrial dysfunction for implantation and early pregnancy. In the present study, we investigated the existence and distribution of calpains, calpastatin, integrin beta3 and alpha-fodrin in decidua from patients with recurrent miscarriage. METHOD OF STUDY: Deciduae were surgically collected from 29 patients with recurrent miscarriage and 20 healthy women with informed consent. Immunohistochemistry, sodium dodecyl sulphate-polyacrylamide gel electrophoresis, and western blot analysis were performed. RESULTS: Staining of mu-calpain, m-calpain, calpastatin, integrin beta3 and alpha-fodrin were observed in the cytoplasm of stromal and epithelial cells in decidua using immunohistochemistry. No significant differences were observed in staining patterns. Western blot analysis showed no significant differences in expression of m-calpain, calpastatin and alpha-fodrin, whereas mu-calpain was significantly higher and integrin beta3 was lower in subject. CONCLUSION: The results suggest that cleavage of integrin beta3 by mu-calpain may have an adverse effect on the mechanism of early pregnancy.

A human DNA polymerase eta complex containing Rad18, Rad6 and Rev1; proteomic analysis and targeting of the complex to the chromatin-bound fraction of cells undergoing replication fork arrest.

DNA polymerase eta (Poleta) is responsible for efficient translesion synthesis (TLS) past cis-syn cyclobutane thymine dimers (TT dimers), the major DNA lesions induced by UV irradiation. Loss of human Poleta leads to xeroderma pigmentosum variant syndrome, clearly indicating that Poleta plays a vital role in preventing skin cancer caused by exposure to sunlight. To further examine Poleta functions and the mechanisms that regulate this important protein, Poleta complexes were purified from HeLa cells over-expressing epitope-tagged Poleta, and polypeptides associated with Poleta, including Rad18, Rad6 and Rev1, were identified by a combination of mass spectrometry and Western blot analysis. The chromatin-bound fractions of cells subjected to UV irradiation, S phase synchronization, or S phase arrest were specifically enriched in such complexes. These results suggest that arrested replication forks strengthen interactions among Poleta, Rad18/Rad6 and Rev1, consistent with the requirement for effective TLS by Poleta at sites of DNA lesions.

Cleavage of integrin by mu-calpain during hypoxia in human endometrial cells.

PROBLEM: The distribution and activation of mu-calpain and possible cleavage of integrin in human endometrial cells under hypoxic condition were investigated. METHOD OF STUDY: Human endometrial epithelial and stromal cells were subjected to hypoxia, and subsequently used for immunostaining and western blot analysis. RESULTS: The proform of mu-calpain was detected in the cytoplasm of normal cells, and displayed a substantial decrease after hypoxia. Conversely, the active form of mu-calpain was not detected in normal cells, but was abundant after hypoxia. The cytoplasmic domain of integrin beta3 was also detected in the cytoplasm of endometrial cells. Western blot analysis confirmed that both the proform of mu-calpain and the integrin beta3 cytoplasmic domain decreased during hypoxia. CONCLUSIONS: Mu-calpain is activated in human endometrial cells during hypoxia and that subsequent cleavage of the integrin beta3 cytoplasmic domain may give some adverse effects to the function of human endometrium.

Distributions of endometrial NK cells, B cells, T cells, and Th2/Tc2 cells fail to predict pregnancy outcome following recurrent abortion.

PROBLEM: To evaluate the ability of immunophenotypes of endometrial leukocytes from patients with histories of recurrent abortion to predict outcome of subsequent pregnancy. METHODS OF STUDY: Seventeen women with two successive spontaneous abortions with normal karyotype in the conceptus and 15 women with male-factor infertility were studied. Subsequent pregnancy outcomes in 17 recurrent abortion patients were noted; 11 had live birth, while six aborted in the first trimester. All of 15 women with male-factor infertility became pregnant after therapy, resulting in live birth in all cases. Endometrium was sampled during the peri-implantation period before subsequent pregnancy. We immunostained paraffin-embedded sections for lymphocyte markers including natural killer (NK) cell markers, CD56 and CD16, a B-cell marker CD20, T-cell markers CD3 and CD8, and a specific T-helper(Th)2 and T-cytotoxic (Tc)2 marker termed 'chemoattractant receptor-homologous molecule expressed on Th2 cells' (CRTH2). Immunoreactive cells for these antigens were counted and positivity ratios to CD45- or CD3-positive cells were calculated. These parameter were compared between 17 patients with histories of recurrent abortion and 15 control women and also compared between 11 patients whose subsequent pregnancy was successful and six patients whose subsequent pregnancy was a failure. RESULTS: Numbers of CD45+, CD56+, CD16+, CD20+, CD3+, CD8+, and CRTH2+ cells in recurrent abortion patients resembled those in controls. No significant difference in lymphocyte subset numbers or ratios was noted between patients whose subsequent pregnancy was successful and those who again aborted. CONCLUSION: We could not predict pregnancy outcome by immunophenotypic analysis of endometrium in women with recurrent abortion.

Identification of protein disulfide isomerase as a phorbol ester-binding protein.

A specific binding protein for 12-O-tetradecanoylphorbol 13-acetate (TPA), different from protein kinase C (PKC) and histone H1, was purified from HeLa cell extract by the use of affinity gel pendanted with phorbol ester (TPA-GEL). The purified binding protein was identified as protein disulfide isomerase (PDI, EC 5.4.3.1) by peptide sequence analysis. The dissociation constants (Kd's) of TPA to PDI, histone H1 and PKCalpha were determined to be 1.03 x 10(-6) M, 5.70 x 10(-7) M, and 4.00 x 10(-7) m, respectively, by the surface plasmon resonance (SPR) method. TPA moderately inhibited PDI activity assessed in terms of reactivation of denatured RNase A.

Novel alpha-glucosidase inhibitors with a tetrachlorophthalimide skeleton.

Novel alpha-glucosidase inhibitors with a tetrachlorophthalimide skeleton were prepared and their structure-activity relationships were analyzed. Among them, N-phenyl-4,5,6,7-tetrachlorophthalimide (CPOP: 2) and N-(4-phenylbutyl)-4,5,6,7-tetrachlorophthalimide (CP4P: 6) showed very potent inhibitory activity, being more potent than 1-deoxynojirimycin (dNM: 1). Mechanistic studies revealed that CPOP (2) and CP4P (6) inhibit alpha-glucosidase non-competitively and competitively, respectively.