Citicoline enhances frontal lobe bioenergetics as measured by phosphorus magnetic resonance spectroscopy.

Citicoline supplementation has been used to ameliorate memory disturbances in older people and those with Alzheimer's disease. This study used MRS to characterize the effects of citicoline on high-energy phosphate metabolites and constituents of membrane synthesis in the frontal lobe. Phosphorus ((31)P) metabolite data were acquired using a three-dimensional chemical-shift imaging protocol at 4 T from 16 healthy men and women (mean +/- SD age 47.3 +/- 5.4 years) who orally self-administered 500 mg or 2000 mg Cognizin Citicoline (Kyowa Hakko Kogyo Co., Ltd, Ibaraki, Japan) for 6 weeks. Individual (31)P metabolites were quantified in the frontal lobe (anterior cingulate cortex) and a comparison region (parieto-occipital cortex). Significant increases in phosphocreatine (+7%), beta-nucleoside triphosphates (largely ATP in brain, +14%) and the ratio of phosphocreatine to inorganic phosphate (+32%), as well as significant changes in membrane phospholipids, were observed in the anterior cingulate cortex after 6 weeks of citicoline treatment. These treatment-related alterations in phosphorus metabolites were not only regionally specific, but tended to be of greater magnitude in subjects who received the lower dose. These data show that citicoline improves frontal lobe bioenergetics and alters phospholipid membrane turnover. Citicoline supplementation may therefore help to mitigate cognitive declines associated with aging by increasing energy reserves and utilization, as well as increasing the amount of essential phospholipid membrane components needed to synthesize and maintain cell membranes.

In vivo selection of Klebsiella pneumoniae strains with enhanced quinolone resistance during fluoroquinolone treatment of urinary tract infections.

We report two cases of failure of fluoroquinolone treatment of urinary tract infections with Klebsiella pneumoniae strains harboring quinolone resistance-associated alterations in GyrA and ParC and in vivo selection of posttreatment isolates with enhanced fluoroquinolone resistance. Active efflux leading to decreased accumulation of a drug enhanced fluoroquinolone resistance in one posttreatment isolate, and an additional mutation in parC resulting in an additional amino acid change in ParC was associated with increased resistance in the other.

Fluoroquinolone treatment failure in gonorrhea. Emergence of a Neisseria gonorrhoeae strain with enhanced resistance to fluoroquinolones.

BACKGROUND AND OBJECTIVES: Although emergence of clinical isolates of Neisseria gonorrhoeae with decreased susceptibilities to fluoroquinolones and treatment failures in gonorrhea have been reported, there have been no clinical reports that fluoroquinolone treatments actually select quinolone-resistant strains, nor have isolates that exhibited clinically significant resistance been analyzed for resistance mechanisms. GOALS: To report a case of fluoroquinolone treatment failure in gonorrhea and emergence of a posttreatment isolate with enhanced resistance to fluoroquinolones; and to study mechanisms of quinolone resistance in the isolates from this patient. STUDY DESIGN: A patient with gonococcal urethritis treated with ofloxacin, 200 mg, three times daily for 5 days is described. Pretreatment and posttreatment isolates were tested for minimum inhibitory concentrations (MICs) of antimicrobial agents and analyzed for alterations in DNA gyrase and topoisomerase IV. They were also examined for ofloxacin uptake. RESULTS: Treatment failure with multiple doses of ofloxacin was observed in this case of gonorrhea. The pretreatment isolate showed decreased susceptibilities to fluoroquinolones (MIC of ofloxacin, 1.0 mg/l; MIC of ciprofloxacin, 0.25 mg/l), and had amino acid changes of Ser-91-->Phe in GyrA and Ser-87-->Ile in ParC. The posttreatment isolate exhibited an increase in resistance to fluoroquinolones (MIC of ofloxacin, 8.0 mg/l; MIC of ciprofloxacin, 1.0 mg/l). This isolate had identical alterations in GyrA and ParC, but exhibited significantly reduced uptake of ofloxacin. This isolate also showed a small decrease in susceptibilities to cephalosporins. CONCLUSIONS: Alterations in DNA gyrase and topoisomerase IV confer clinically significant resistance to fluoroquinolones in N. gonorrhoeae strains. Treatment with multiple doses of fluoroquinolones is likely to bring about selection of more fluoroquinolone-resistant strains of N. gonorrhoeae and to influence susceptibilities to cephalosporins.

Comparison of complicated urinary tract infections in men and women.

Whether or not the efficacy of antimicrobial agents in complicated urinary tract infection (UTI) in men and women can be evaluated with the same protocol was studied in a total of 416 male and 387 female patients. Clinical and bacteriological efficacies achieved in male patients were significantly lower than those achieved in female patients. The most important reason for the difference in clinical and bacteriological efficacies was due to the difference of infecting organisms between male and female patients. It was concluded that complicated UTI in men and women can alternatively be studied with the same protocol in so far as the results were stratified according to sex and infecting organism.

Antitumor activity of a new platinum complex, oxalato (trans-l-1,2-diaminocyclohexane)platinum (II): new experimental data.

Antitumor activity of a new platinum complex, oxalato (trans-l-1,2-diaminocyclohexane) platinum (II) (l-OHP), was studied. This water-soluble platinum complex showed a more prominent life-prolonging effect on a mouse leukemia L1210 than cisplatin (DDP). By an intermittent treatment schedule cured mice were observed at the optimal dose. In addition, a subline of L1210 having a 40-fold resistance to DDP (L1210/DDP) showed lack of cross-resistance to l-OHP both in vivo and in vitro. Especially in vivo l-OHP was more active against L1210/DDP than against the original L1210, and all mice were cured at doses of 6.25 and 3.12 mg/kg. l-OHP was also effective against several mouse tumors such as P388 leukemia, B16 melanoma, Lewis lung carcinoma, colon 26 and colon 38 adenocarcinomas, and M5076 fibrosarcoma, though its antitumor spectrum was somewhat different from that of DDP. The synthesis of both DNA and RNA in L1210 cells was inhibited by about 50% with exposure to 10 microM of l-OHP for 1 h, followed by postincubation in drug-free medium for 6-24 h, while only the inhibition of DNA synthesis was observed by DDP in the same experiment. If severe toxicity is not observed in preclinical study, l-OHP expected to be a new clinically active Pt complex.

[Primary carcinoid tumor of the testis: a case report].

A case of pure, primary testicular carcinoid tumor in a 27-seven-year-old male is reported. The patient presented with a painless enlargement of the right testis but the serum markers for testicular cancer, including alpha-fetoprotein, beta-human chorionic gonadotropin and lactate dehydrogenase, were not elevated. Right orchiectomy was performed. Histologically, the tumor showed a typical appearance of carcinoid tumor. Further examinations such as barium studies, computed tomographic scan and Ga scintigraphy, showed no other lesions, and he received an adjuvant chemotherapy of cyclophosphamide, 5-fluorouracil and adriamycin. He is well and free from symptoms 17 months after surgery.

[A case of vesicosigmoidal fistula secondary to diverticulitis of the colon].

A case of vesicosigmoidal fistula secondary to the diverticulitis of colon is reported. A 63-year-old man was admitted to our clinic with the chief complaint of pneumaturia. Cystoscopy revealed an edematous, papillomatous lesion at the left posterior bladder wall. Although multiple diverticulosis of descending and sigmoid colon were demonstrated by barium enema, the presence of a fistula from the intestine to bladder was not confirmed. The presence of fistula was confirmed by detecting the orally administered charcoal in the urine. Resection of sigmoid colon with partial cystectomy was performed. Removed specimen revealed multiple sigmoidal diverticula and a fistula from a sigmoidal diverticulum to bladder through a firm mass. Histological examination of mass demonstrated inflammatory changes. This was the 58th case of vesicosigmoidal fistula due to diverticulitis of colon reported in the Japanese literature.

Corticotropin-releasing factor (CRF) and vasopressin concentration in major brain regions after adrenalectomy and their involvement in adrenalectomy-induced ACTH elevation.

CRF and vasopressin concentrations in major brain regions after bilateral adrenalectomy and their involvement in adrenalectomy-induced ACTH secretion were investigated. At 5, 14 and 28 days after bilateral adrenalectomy, the plasma ACTH level was greatly elevated, whereas hypothalamic CRF content was reduced at 5 days and was not changed at 14 and 28 days after adrenalectomy. The CRF concentration in the medulla oblongata was reduced at 2-4 weeks after adrenalectomy. On the other hand, the arginine vasopressin (AVP) concentration was significantly elevated 2-4 weeks after adrenalectomy. An intrajugular administration of anti-ovine or anti-rat CRF serum significantly suppressed the elevated plasma ACTH level in adrenalectomized, freely moving rats, whereas anti-AVP serum or antipressor AVP antagonist, dpTyr(Me)AVP did not suppress the ACTH level. These results indicate that CRF played an important role in the adrenalectomy-induced ACTH elevation but that vasopressin was not involved.

Stability of rat (human) corticotropin-releasing factor in serum, urine and tissue incubation medium.

The stability of rat (human) CRF in serum, urine and tissue incubation medium was examined using Sephadex gel filtration and CRF radioimmunoassay with anti-rat (human) CRF serum. Human serum after incubation with rat (human) CRF for 1 h at 37 degrees C showed two peaks of CRF immunoreactivity on a Sephadex G-50 fine column. Most of the immunoreactivity coeluted with the rat (human) CRF marker. When rat (human) CRF was incubated with rat liver, kidney or hypothalamus, only 3.1-14.9% of the CRF was recovered at the rat (human) CRF position on gel filtration, and two to four CRF-immunoreactive peaks appeared after the rat (human) CRF marker. When rat (human) CRF was incubated with human urine (pH 6.0) for 24 h at room temperature, one peak of CRF immunoreactivity coeluted with the rat (human) CRF marker on Sephadex gel filtration. The urine extracts of normal rats showed some small peaks of CRF-like immunoreactivity on the Sephadex column, with the main peak appearing after authentic CRF. These results suggest that rat (human) CRF is relatively stable in serum and urine, but is easily degraded by tissue enzymes, with the degraded CRF fragments being excreted in the urine.

Treatment of metastatic gastric cancer by combined radiation and hyperthermia (report of two cases).

Two patients with metastatic carcinoma of the stomach on the abdominal wall were treated by radiotherapy using cobalt-60 gamma-ray or megavoltage electrons combined with hyperthermia induced with a Thermotron (8 MHz). The total dosage was 44 Gy fractionated into 11 doses (twice a week), by cobalt-60 gamma-ray and 10 hyperthermia treatments for patient 1, and 32 Gy fractionated into eight doses (twice a week) given by megavoltage electrons and five hyperthermia treatments for patient 2. In patient 1, the shrinkage of the tumor was more than 50%. No tumor cells were observed histologically at the end of treatment. In patient 2, the tumors completely disappeared. These results encourage us in the use of radiotherapy combined with hyperthermia for rather radioresistant adenocarcinoma.

Trials of combined radiation and hyperthermia with various heating modalities in cancer therapy.

A microwave heating apparatus with a frequency of 2,450 MHz and an inductive radio-frequency heating apparatus were developed for hyperthermia for cancer therapy, and clinical trials of combined radiation and hyperthermia were conducted. During the same period, a capacitive type radiofrequency unit was used. The tumors included superficial tumors, cancer of the uterine cervix, recurrent tumors at the stump of the cervix, and some deep-seated tumors. Cases showing complete response were as follows: 5 out of 13 cases treated with 2,450 MHz heating for superficial tumors, 8 out of 17 cases treated with 2,450 MHz intracavitary heating, and 2 out of 15 cases treated with radiofrequency heating. A feasibility study of various heating modalities was performed.

Angiography before and after radiotherapy for a thalamic tumor.

A patient with a thalamic tumor received radiotherapy. A right cerebral angiogram seven days after the irradiation was finished revealed increased vascularity, early filled deep cerebral veins and signs of increased mass. A subsequent angiogram showed gradual regression of these features. There is no literature on angiographic progression with early venous filling following radiotherapy.