Exocytosis of gold nanoparticle and photosensitizer from cancer cells and their effects on photodynamic and photothermal processes.

We first illustrate the faster decrease of the photothermal (PT) effect with the delay time of laser treatment, in which the illumination of a 1064 nm laser effectively excites the localized surface plasmon (LSP) resonance of cell-up-taken gold nanoring (NRI) linked with a photosensitizer (PS), when compared with the photodynamic (PD) effect produced by the illumination of a 660 nm laser for effective PS excitation. The measurement results of the metal contents of Au NRI and PS based on inductively coupled plasma mass spectroscopy and the PS fluorescence intensity based on flow cytometry show that the linkage of NRI and PS is rapidly broken for releasing PS through the effect of glutathione in lysosome after cell uptake. Meanwhile, NRI escapes from a cell with a high rate such that the PT effect decays fast while the released PS can stay inside a cell longer for producing a prolonged PD effect. The effective delivery of PS through the linkage with Au NRI for cell uptake and the advantageous effect of LSP resonance at a PS absorption wavelength on the PD process are also demonstrated.

Prevention of perceptual-motor decline by branched-chain amino acids, arginine, citrulline after tennis match.

Perceptual-motor performance in prolonged tennis matches may be affected by central fatigue. The purpose of this study was to investigate the supplementation of branched-chain amino acids (BCAA), arginine, and citrulline on tennis-specific perceptual-motor performance after a simulated match. Nine male tennis players consumed 0.17 g/kg BCAA, 0.05 g/kg arginine, and 0.05 g/kg citrulline (AA trial), or placebo (PB trial) 1 h before the match. In the perceptual-motor performance test before and after the match, the subjects hit balls to the opposite direction of the examiner's movement. The AA trial showed significantly higher rate of correct direction than the PB trial after the match (AA trial: 93.63 ± 1.28%, PB trial: 69.09 ± 2.40%). The AA trial also demonstrated significantly higher post-match accuracy and consistency than the PB trial. The AA trial showed significantly lower heart rate and ratings of perceive exertion during the match, concurrently with a significantly lower plasma total tryptophan/BCAA ratio. Similar post-match plasma NH3 concentrations were found in both trials while the AA trial was significantly higher in NOx concentration. This study suggested that the supplementation could prevent the decline in perceptual-motor performance through alleviation of central fatigue by BCAA and prevention of excess hyperammonemia by arginine and citrulline.

Combination of photothermal and photodynamic inactivation of cancer cells through surface plasmon resonance of a gold nanoring.

We demonstrate effective inactivation of oral cancer cells SAS through a combination of photothermal therapy (PTT) and photodynamic therapy (PDT) effects based on localized surface plasmon resonance (LSPR) around 1064 nm in wavelength of a Au nanoring (NRI) under femtosecond (fs) laser illumination. The PTT effect is caused by the LSPR-enhanced absorption of the Au NRI. The PDT effect is generated by linking the Au NRI with the photosensitizer of sulfonated aluminum phthalocyanines (AlPcS) for producing singlet oxygen through the LSPR-enhanced two-photon absorption (TPA) excitation of AlPcS. The laser threshold intensity for cancer cell inactivation with the applied Au NRI linked with AlPcS is significantly lower when compared to that with the Au NRI not linked with AlPcS. The comparison of inactivation threshold intensity between the cases of fs and continuous laser illuminations at the same wavelength and with the same average power confirms the crucial factor of TPA under fs laser illumination for producing the PDT effect.

Low-level laser therapy alleviates mechanical and cold allodynia induced by oxaliplatin administration in rats.

PURPOSE: Cold and mechanical allodynia caused by oxaliplatin-induced acute peripheral neuropathy frequently occur after drug infusion. Low-level laser therapy (LLLT) has been used to improve pain symptoms associated with various conditions and may have potential as a therapy for oxaliplatin-induced allodynia. The purpose of the present study was to investigate the antiallodynic effect of LLLT in an oxaliplatin-treated animal model by assessing sensory behavioral responses, levels of nerve growth factor (NGF), and transient receptor potential M8 (TRPM8) in dorsal root ganglia (DRG) neurons, as well as substance P (SP) in the spinal dorsal horn. METHODS: Adult male Sprague-Dawley rats each received a total of four doses of oxaliplatin (4 mg/kg, i.p.), injected at 3-day intervals. Following oxaliplatin administration, LLLT (7.5 J/cm(2)) was applied for 12 consecutive days to the skin surface directly above sites where the sciatic nerve is distributed. Behavioral assessments were then performed, followed by immunoassays for NGF, TRPM8, and SP proteins. RESULTS: LLLT relieved both cold and mechanical allodynia induced by oxaliplatin in rats. Oxaliplatin-related increases in protein levels of NGF and TRPM8 in DRG and SP in the dorsal horn were also reduced after LLLT. CONCLUSION: The findings of this study support LLLT as a potential treatment for oxaliplatin-induced neuropathy. Moreover, our findings suggest that SP, TRPM8, and NGF proteins in the superficial dorsal horn and DRG may be involved in an antiallodynic effect for LLLT.

On-substrate fabrication of a bio-conjugated Au nanoring solution for photothermal therapy application.

The on-substrate fabrication of a bio-conjugated Au nanoring (NRI) solution with the localized surface plasmon (LSP) resonance wavelength in the 1200-1300 nm range is demonstrated. Also, the effects of photothermal therapy through LSP resonance-induced absorption enhancement are illustrated by applying the bio-conjugated Au NRIs to human liver cancer cells and illuminating the cells with a laser of 1315 nm in wavelength. The Au NRI fabrication is based on the techniques of nano-imprint lithography and metal secondary sputtering. The procedure for on-substrate surface modification of Au NRIs leads to a high production yield of bio-conjugated NRIs. The threshold levels of the local laser intensity for injuring cancer cells based on the LSP resonances of Au NRIs of two different samples are determined.

Randomized multicenter clinical trial of myofascial physical therapy in women with interstitial cystitis/painful bladder syndrome and pelvic floor tenderness.

PURPOSE: We determined the efficacy and safety of pelvic floor myofascial physical therapy compared to global therapeutic massage in women with newly symptomatic interstitial cystitis/painful bladder syndrome. MATERIALS AND METHODS: A randomized controlled trial of 10 scheduled treatments of myofascial physical therapy vs global therapeutic massage was performed at 11 clinical centers in North America. We recruited women with interstitial cystitis/painful bladder syndrome with demonstrable pelvic floor tenderness on physical examination and a limitation of no more than 3 years' symptom duration. The primary outcome was the proportion of responders defined as moderately improved or markedly improved in overall symptoms compared to baseline on a 7-point global response assessment scale. Secondary outcomes included ratings for pain, urgency and frequency, the O'Leary-Sant IC Symptom and Problem Index, and reports of adverse events. We compared response rates between treatment arms using the exact conditional version of the Mantel-Haenszel test to control for clustering by clinical center. For secondary efficacy outcomes cross-sectional descriptive statistics and changes from baseline were calculated. RESULTS: A total of 81 women randomized to the 2 treatment groups had similar symptoms at baseline. The global response assessment response rate was 26% in the global therapeutic massage group and 59% in the myofascial physical therapy group (p=0.0012). Pain, urgency and frequency ratings, and O'Leary-Sant IC Symptom and Problem Index decreased in both groups during followup, and were not significantly different between the groups. Pain was the most common adverse event, occurring at similar rates in both groups. No serious adverse events were reported. CONCLUSIONS: A significantly higher proportion of women with interstitial cystitis/painful bladder syndrome responded to treatment with myofascial physical therapy than to global therapeutic massage. Myofascial physical therapy may be a beneficial therapy in women with this syndrome.

28-day oral toxicity study of the aqueous extract from spider brake (Pteris multifida Poiret) in rats.

Spider brake (Pteris multifida Poiret) is a very important folk herb and a constituent in most of the traditional herbal beverage formulas in Taiwan; however, little toxicological information is available regarding the safety following repeated exposure. The present study was conducted to evaluate the toxicity of aqueous extract from spider brake (SB) in Sprague-Dawley rats on dietary oral gavage at concentrations of 100, 500, and 1000 mg/kg b.w. day for 28 days. There were no adverse effects on general condition, growth, feed and water consumption, feed conversion efficiency, red blood cell and clotting potential parameters, clinical chemistry values, and organ weights except for neutrophils and lymphocytes being slightly diminished in male and female rats at the highest dose, respectively. Necropsy and histopathology findings revealed no treatment-related changes in any of the organs. The results obtained in this study allowed us to conclude that the SB properly utilized in the traditional oral administration could be devoid of any toxic risk.

Free radical-scavenging activity of aqueous extract of Pteris multifida Poiret.

Aqueous extract of Pteris multifida showed scavenging activities on DPPH, hydroxyl radicals and reducing power.

Effect of hyperbaric oxygen on cardiac neural regulation in diabetic individuals with foot complications.

AIMS: There are relatively few effective methods to treat autonomic neuropathy in patients with diabetes mellitus. Our aim was to test the hypothesis that hyperbaric oxygen therapy may restore cardiac neural regulation dysfunction in diabetic individuals with foot complications. METHODS: We conducted a prospective randomized controlled study in patients with diabetic foot problems. Daily heart-rate variability analysis from 5-min electrocardiography was used to evaluate the temporal change of cardiac neural regulation. The experimental group consisted of 23 subjects exposed to hyperbaric oxygen therapy of 202.65 kPa for 90 min every Monday to Friday for 4 weeks (20 treatments). The control group consisted of 15 age-, sex- and disease-matched subjects who were not exposed to hyperbaric therapy. Patients with medical complications and failure of wound healing were excluded to eliminate possible confounding effects. RESULTS: There was no significant difference in baseline R-R interval (RR), variance, high-frequency power (HF), low-frequency power (LF), and LF/HF ratio between the two groups. In the hyperbaric oxygen group there were significant increases in changes of RR (82.7 +/- 16.02 ms); variance 0.88 +/- 0.12 ln(ms2); HF 1.06 +/- 0.18 ln(ms2); and LF 0.87 +/- 0.15 ln(ms2) after the treatment. Measurements of tissue oxygen demonstrated significant increases in local tissue oxygenation in the hyperbaric oxygen group (53.0 +/- 2.6 mmHg) compared with the control group (27.5 +/- 3.1 mmHg), P < 0.05. CONCLUSION: Hyperbaric oxygen therapy has a significant vagotonic effect, which is beneficial in improving cardiac neural regulation in patients with diabetic autonomic dysfunction.

Effects of garlic components diallyl sulfide and diallyl disulfide on arylamine N-acetyltransferase activity and 2-aminofluorene-DNA adducts in human promyelocytic leukemia cells.

Two components of garlic, diallyl sulfide (DAS) and diallyl disulfide (DADS), inhibited arylamine N-acetyltransferase (NAT) activity and 2-aminofluorene-DNA adduct in human promyelocytic leukemia cells (HL-60). The NAT activity was measured by high performance liquid chromatography assaying for amounts of N-acetyl-2-aminofluorene (2-AAF) and remaining 2-aminofluorene (2-AF). Cellular cytosols and intact cell suspensions were assayed. The inhibition of NAT activity and 2-AF-DNA adduct formation in human leukemia cells by DAS and DADS were dose-dependent and were directly proportional. The data also indicated that DAS and DADS decrease the apparent values of Km and Vmax from human leukemia cells in both assays. This is the first report of garlic components affecting human leukemia cell NAT activity and 2-AF-DNA adduct formation.

Acute toxicities of betel nut: rare but probably overlooked events.

BACKGROUND: Betel nut chewing has long been a social habit in Taiwan and other Asian and tropical countries. It produces various autonomic and psychoneurologic effects including tachycardia, flushing, warmth, cholinergic activation, alertness, and euphoria. Although the oral carcinogenic effects are well known, data concerning its acute toxicity are few. To better understand the toxicity of betel nut, cases reported to the Taiwan Poison Control Center as probable or possible betel nut-related toxicity (January 1988-June 1998) were reviewed. In the 17 cases suitable for review (14 males, 3 females, age 21 to 60 years), the most common manifestations were tachycardia/palpitations (7); tachypnea/dyspnea (6); hypotension and sweating (5); vomiting, dizziness, and chest discomfort (4); abdominal colic, nausea, numbness, and coma (3); and acute myocardial infarction and related manifestations (2). The reported quantity of betel nut used was low (1 to 6 nuts), except an extract of 100 betel nuts was used in 1 case and 66 chewed in another. Most cases recovered within 24 hours after the exposure. One patient developed probable acute myocardial infarction and ventricular fibrillation and died despite repeated cardiac defibrillation. Although betel nut chewing is widespread, significant toxicity as reported to a poison center is rare. Because most betel nut-related effects are transient and mild in nature, the incidence of such events is likely to be underreported. Nevertheless, betel nut chewing can produce significant cholinergic, neurological, cardiovascular, and gastrointestinal manifestations. It is possible that it may aggravate cardiac diseases in susceptible patients but this hypothesis must be further investigated. Treatment is symptomatic. With timely support, rapid and complete recovery is anticipated but a small risk of major complications cannot yet be discounted.

Bladder management in women with neurologic disabilities.

Women with neurologic disabilities can experience an array of bladder disorders. There are many aspects of lower urinary tract management that are specific to women. Treatments should be based on urodynamic findings, and individualized for each woman's physical and cognitive abilities.

Antegrade continence enema for the treatment of neurogenic constipation and fecal incontinence after spinal cord injury.

OBJECTIVE: To describe the effects of an antegrade continence enema stoma formed in a paraplegic man with intractable constipation and fecal incontinence. DESIGN: Case report. SETTING: Spinal cord injury unit, Veterans Affairs hospital. PARTICIPANTS: Spinal cord injury (SCI) patient with T12 paraplegia. INTERVENTION: Surgical formation of antegrade continence enema stoma. MAIN OUTCOME MEASURES: Time of bowel program care, ease of fecal elimination, safety of procedure. RESULTS: Bowel care time was decreased from 2 hours to 50 minutes daily; 6 bowel medications were discontinued; fecal incontinence was eliminated; and no surgical or medical side effects noted after the procedure. CONCLUSION: The antegrade continence enema procedure is a safe and effective means of treating intractable constipation and fecal incontinence in the adult SCI patient. This option should be considered for those persons in whom medical management of bowel care has been unsuccessful.

Antisense suppression of proline-directed protein kinase FA enhances chemosensitivity in human prostate cancer cells.

Initial clinic studies revealed that proline-directed protein kinase FA (PDPK FA) is overexpressed manyfold in various human cancerous tissues relative to the normal control. However, the role of overexpressed PDPK FA in cancers remains unknown and needs to be established. To determine whether PDPK FA is associated with drug sensitivity, we investigated the effects of partial inhibition of this kinase on the human prostate carcinoma cell line (PC-3). PDPK FA antisense expression vector and its specific antibody were successfully developed. Two stable transfected antisense clones (PA7 and PA3) of human prostate carcinoma cell were subcloned, and they expressed approximately 75% and approximately 35% of the total PDPK FA existing in the control-transfected clone as determined by both immunoprecipitate activity assay and immunoblot analysis. In sharp contrast, the PDPK FA antisense clones expressed no significant suppression of any other related proline-directed protein kinase member expression, demonstrating the specificity of these two antisense clones. When compared with parental or control-transfected cells, the low-PDPK FA-expressing antisense clones displayed an enhanced sensitivity to carboplatin, 5-fluorouracil, paclitaxel, and hydroxyurea. Estimation of the IC50 index further revealed that the antisense clones displayed up to > 100-fold drug sensitivity, and there was a correlation between suppressed levels of PDPK FA and drug sensitivity. Taken together, the results demonstrate that specific antisense suppression of overexpressed PDPK FA in human prostate cancer cells is sufficient to enhance various drug sensitivity, indicating that PDPK FA is an important regulator in controlling multiple drug resistance of human prostate cancer cells.

Cardiac arrhythmia and betel nut chewing--is there a causal effect?

Betel nuts are widely ingested in many countries, including Taiwan. They stimulate various autonomic and CNS reactions, but there have been no reports of cardiac toxicity. We treated 2 patients with cardiac dysrhythmias thought due to betel nut chewing. In case 1, a 44-y-old previously healthy male presented with chest tightness, dyspnea, diaphoresis and palpitation immediately after chewing 1 betel quid. He soon became breathless and died despite immediate cardiopulmonary resuscitation. In Case 2, a 28-y-old man suffered palpitations, epigastralgia, and chest distress following consumption of 4 betel quid. Paroxysmal supraventricular tachycardia was noted and terminated by repeated verapamil administration. The pharmacological properties of betel nuts and the time sequence of these cases raise the possibility of betel nut-induced cardiac dysrhythmias. The number of betel nut chewers in Taiwan continues to increase, suggesting there may be other cases of betel nut-related cardiac toxicities in the future.

Adult Fanconi syndrome with proximal muscle weakness and hypophosphatemic osteomalacia: report of a case.

A 42-year-old female presented with progressive proximal muscle weakness, generalized hyperreflexia, marked bone pain, severe lumbago and knee arthralgia. Electromyographic study showed short-duration (5-10 msec), variable amplitude (200-2500 microV) polyphasic potentials. A muscle biopsy specimen revealed non-specific type II fiber atrophy. After a comprehensive laboratory work-up, adult Fanconi syndrome was diagnosed. The patient's symptoms, including bone pain and proximal muscle weakness, were relieved after a six-week supplement of tricalcium phosphate, vitamin D3 and sodium bicarbonate. The hyperreflexia also became less brisk.

The pharmacological and pathological studies on several hepatic protective crude drugs from Taiwan (II).

Four crude drug extracts of Solanum incanum (entire plant), Ixeris chinensis (entire plant), Gardenia jasminoides (wild and cultivated, fructus) were administered to rats as dose of 1.0 g/kg, I.P. injection to screen the liver protective effect on CC14 induced hepatotoxicity. The acute increase of transaminase SGOT and SGPT levels that was caused by CC14 (1.0 ml/kg) S.C. injection can be significantly improved when treated with Solanum incanum (p less than 0.005), Ixeris chinensis (p less than 0.001), Gardenia jasminoides (cultivated) (p less than 0.005) but only a moderate change was shown by means of wild Gardenia jasminoides (p less than 0.05). As our results indicated, the extraction of these drugs has been found to possess a marked hepatic protective effect. The hepatic fatty metamorphosis and necrosis of central lobule were obviously improved by S. incanum and I. chinensis, administration, while the effect of treatment with G. jasminoides (cultivated) demonstrated a moderate protective action and little histopathological change by G. jasminoides (wild). In contrast to B. chinese, which has been reported previously as a treatment criteria, the S. incanum (p less than 0.01) and I. chinensis (p less than 0.01) in the present study have indicated that a significantly different hepatic protective effect on CC14 induced hepatic injury.

The pharmacological and pathological studies on several hepatic protective crude drugs from Taiwan (I).

This study is to investigate the hepatic protective effect of several Taiwan crude drug extractions on the carbon tetrachloride (CCl4)-induced hepatotoxicity in rats. The pharmacological and pathological effects of Bupleurum chinense, Phellodendron wilsonii, Clematis chinensis and Hedyotis corymbosa were analyzed by liver enzyme function test and pathological studies. However, the results of amine transferase SGOT and SGPT have shown a significant hepatic protective effect after treatment with Bupleurum chinense (P less than 0.005), Phellodendron wilsonii (P less than 0.001), Clematis chinensis (P less than 0.005) and Hedyotis corymbosa (P less than 0.005, SGPT only). The fatty degeneration around the central vein area and necrosis of the central lobule can be significantly improved by P. wilsonii and moderately changed by B. chinense or C. chinensis. Although fatty metamorphosis has been affected by H. corymbosa, various inflammatory cell infiltrations in the cytoplasm were noted.