Effect of gamma irradiation on phenol content, antioxidant activity and biological activity of black maca and red maca extracts (Lepidium meyenii walp).

This study was performed to determine the effects of gamma irradiation on UV spectrum on maca, total content of polyphenols, 1,1-diphenyl-2-picrylhydrazyl (DPPH) radical-scavenging activities and in vivo biological activities of red and black maca extracts (Lepidium meyenii). Adult mice of the strain Swiss aged 3 months and weighing 30-35 g in average were used to determine biological activities. Daily sperm production, effect on testosterone-induced prostate hyperplasia and forced swimming test were used to determine the effect of irradiation on biological activities of maca extracts. Irradiation did not show differences in UV spectrum but improves the amount of total polyphenols in red maca as well as in black maca extracts. In both cases, black maca extract has more content of polyphenols than red maca extract (p < 0.01). Gamma irradiation significantly increased the antioxidant capacity (p < 0.05). No difference was observed in daily sperm production when irradiated and nonirradiated maca extract were administered to mice (p > 0.05). Black maca extract but not red maca extract has more swimming endurance capacity in the forced swimming test. Irradiation of black maca extract increased the swimming time to exhaustion (p < 0.05). This is not observed with red maca extract (p > 0.05). Testosterone enanthate (TE) increased significantly the ventral prostate weight. Administration of red maca extract in animals treated with TE prevented the increase in prostate weight. Irradiation did not modify effect of red maca extract on prostate weight (p > 0.05). In conclusion, irradiation does not alter the biological activities of both black maca and red maca extracts. It prevents the presence of microorganisms in the extracts of black or red maca, but the biological activities were maintained.

Sudden Vegetation Dieback in Atlantic and Gulf Coast Salt Marshes.

Salt marshes rank as the most productive ecosystems on the planet. Biomass production can be greater than 3 kg dry matter/m2/year, which is 40% more biomass than tropical rainforests produce. Salt marshes provide multiple benefits to mankind. For example, coastal communities receive protection from storm surges and wave erosion. Salt marshes absorb excess nitrogen and phosphorus from sewage and fertilizer run-off into rivers, which, in turn, prevents algal blooms and hypoxia in coastal waters. In addition, these unique ecosystems provide habitat and shelter for many hundreds of species of shellfish, finfish, migratory and sedentary birds, and other marine animals. Despite the richness in animal species, the intertidal marshes of the salt marsh ecosystem are dominated by only a few plant species. Of these, the most prevalent plant species in a marsh are the tall and short forms of smooth cordgrass (Spartina alterniflora). The first recorded account of a dieback in a U.S. salt marsh was in the early 1990s in the Florida panhandle where patches of Sp. alterniflora as large as 1 ha died. This article explores possible causes of Sudden Vegetation Dieback.

Aromatase activity after a short-course of letrozole administration in adult men at sea level and at high altitude (with or without excessive erythrocytosis).

Men living at high altitudes in Peru compared to sea level counterparts have erythrocytosis (hemoglobin 16-21 g/dl) or excessive erythrocytosis (hemoglobin>21 g/dl). High testosterone (T) levels in men at high altitude (HA) were associated with excessive erythrocytosis. High androgen levels could be due to a low aromatase activity or to an elevated rate of conversion from precursors to testosterone. The aim of this study was to evaluate aromatase activity and rate of conversion from precursors to testosterone before and after administration of the aromatase enzyme inhibitor letrozole (5 mg/day) for a 5-day period to men at HA and at sea level (SL). The response to short term aromatase inhibition was assessed in 30 adult men living at sea level, 31 native men at HA with erythrocytosis (Hb 16-21 g/dl), and 35 men at HA with excessive erythrocytosis (Hb>21 g/dl). Serum hormone levels, estradiol/testosterone, testosterone/androstenedione, and testosterone/dehydroepiandrosterone sulfate (DHEAS) ratios were measured. Men with erythrocytosis had lower basal serum T/androstenedione ratios than men with excessive erythrocytosis at HA and men at sea level. Men at HA with excessive erythrocytosis had higher T/DHEAS ratios than men with erythrocytosis and than those at sea level before and after letrozole administration. After letrozole administration, both groups of men at high altitude (with erythrocytosis or with excessive erythrocytosis) showed lower aromatase activities than those at sea level. In conclusion, higher serum testosterone levels in men with excessive erythrocytosis were associated with an increased rate of conversion from DHEAS to testosterone rather than to a lower aromatase activity.

Resistance of sperm motility to serum testosterone in men with excessive erythrocytosis at high altitude.

Excessive erythrocytosis (EE) [hemoglobin (Hb) >21 g/dl] observed in natives at high altitude (HA) seems to be due to elevated serum testosterone levels compared with men without EE at HA. The aim of the study was to determine the association between serum testosterone levels and high hemoglobin levels at HA with sperm quality. The study was conducted with 72 adult men living at 4,340 m and 52 native men at sea level (SL). At HA, men were grouped according to hemoglobin value (group 1:16-21 g/dl or group 2: Hb >21 g/dl). Hemoglobin and serum testosterone levels were evaluated. Sperm concentration, percentage of progressive sperm motility, percentage of normal sperm morphology, and markers of seminal vesicles function (corrected seminal fructose) and of prostate function (seminal zinc levels) were calculated. Serum testosterone levels were significantly higher in the group with EE (p<0.001). Progressive sperm motility in men with EE was lower than in the other group (Hb >16-21 g/dl) and that of those at SL. Seminal pH, zinc levels and normal sperm morphology in men at HA were lower than at SL. At HA, a significant inverse relationship was observed between hemoglobin and progressive sperm motility (p<0.01). At SL, serum testosterone levels were directly related with progressive sperm motility, whereas at HA, no association was observed (p>0.05). No association between testosterone levels and corrected seminal fructose was observed in men with EE. In conclusion, low sperm motility was observed in men with EE despite elevated serum testosterone levels suggesting a resistance of sperm motility.

Effect of red maca (Lepidium meyenii) on prostate zinc levels in rats with testosterone-induced prostatic hyperplasia.

Lepidium meyenii (maca) is a plant that grows exclusively above 4000 m in the Peruvian central Andes. Red maca (RM) extract significantly reduced prostate size in rats with benign prostatic hyperplasia (BPH) induced by testosterone enanthate (TE). Zinc is an important regulator of prostate function. This study aimed to determine the effect of RM on prostate zinc levels in rats with BPH induced by TE. Also, the study attempted to determine the best marker for the effect of RM on sex accessory glands. Rats treated with RM extract from day 1 to day 14 reversed the effect of TE administration on prostate weight and zinc levels. However, RM administered from day 7 to day 14 did not reduce the effect of TE on all studied variables. Finasteride (FN) reduced prostate, seminal vesicle and preputial gland weights in rats treated with TE. Although RM and FN reduced prostate zinc levels, the greatest effect was observed in TE-treated rats with RM from day 1 to day 14. In addition, prostate weight and zinc levels showed the higher diagnosis values than preputial and seminal vesicle weights. In conclusion, RM administered from day 1 to day 14 reduced prostate size and zinc levels in rats where prostatic hyperplasia was induced with TE. Also, this experimental model could be used as accurately assay to determine the effect of maca obtained under different conditions and/or the effect of different products based on maca.

Evaluation of different doses of mashua (Tropaeolum tuberosum) on the reduction of sperm production, motility and morphology in adult male rats.

Mashua is an edible-tuber crop that grows in the Andean region. Folk medicine describes the use of mashua to reduce reproductive function in men. The present study aimed: (i) to determine whether different doses of mashua (0.01, 0.1, 1 and 2 g kg(-1)) produced a dose-response reduction on sperm production and quality; and, (ii) to determine whether these anti-reproductive effects of mashua can be reversible after cessation of treatment (12 and 24 days of recovery time). Mashua-treated rats showed lower values of daily sperm production, epididymal and vas deferens sperm count and sperm motility; meanwhile, mashua increased the percentage of abnormal sperm morphology and epididymal sperm transit rate. The following variables follow a dose-response effect: sperm number in vas deferens, sperm motility and sperm transit rate. In addition, it was demonstrated that the reduction in reproduction function in male rats treated with mashua was reversible after 24 days of recovery time. Finally, lower doses mashua reduces sperm number and quality (motility and morphology), and these adverse effects on male reproductive system may be reversible after 24 days after cessation of the treatment.

Cisplatin-based chemoradiation plus cetuximab in locally advanced head and neck cancer: a phase II clinical study.

BACKGROUND: Intensification of chemoradiation for advanced head and neck squamous cell carcinoma (HNSCC) is unlikely due to toxicity. Cetuximab combined either with radiotherapy or with chemotherapy showed favourable toxic profile with positive results in both combinations. Therefore, cetuximab could intensify chemoradiation without worsening toxicity. We conducted a phase II study of chemoradiation and cetuximab. PATIENTS AND METHODS: Eligible patients had stage III-IV M0 HNSCC. Treatment consisted of three cycles of cisplatin (20 mg/m(2)/day × 5 days) and fluorouracil (200 mg/m(2)/day × 5 days) rapidly alternated to three split courses of radiotherapy up to 70 Gy and concurrent weekly cetuximab. The primary end point of the study was complete response (CR) rate. Secondary end points were toxicity, progression-free survival (PFS) and overall survival (OS). RESULTS: Fourty-five patients were enrolled: median age was 56 years, 38 had stage IV disease and 40 nodal involvement. CR occurred in 32 patients (71%). PFS and OS was 21+ months and 32.6+, respectively. Acute grade 3-4 toxic effects were in the expected range, but grade 3 radiodermatitis occurred in 33 patients. CONCLUSIONS: The combination of cetuximab, cisplatin, fluorouracil and radiotherapy leads to a very high proportion of CR and it is feasible with toxic effects similar to those expected by radiochemotherapy. The only unexpected toxicity was skin toxicity: grade 3 radiodermatitis occurred in 73% of the patients.

Serum testosterone levels and score of chronic mountain sickness in Peruvian men natives at 4340 m.

Life at high altitudes (>4000 m) is associated with higher erythropoiesis. Haemoglobin ≥21 g dl(-1) is considered as excessive erythrocytosis and is a sign of chronic mountain sickness (CMS). The present study was designed to determine an association between serum testosterone (T) and serum oestradiol (E(2) ) levels with the score of CMS. One hundred and seventeen men natives from low altitude (150 m) and 103 men natives from high altitude (4340 m) were studied. The presence of breathlessness or palpitations, sleep disturbance, cyanosis, dilatation of veins, paraesthesia, headaches, tinnitus and Hb ≥21 g dl(-1) , have been included for the CMS score. Men living at high altitude had higher CMS score (P < 0.001), serum T (P < 0.05) and serum E(2) levels (P < 0.04) and had lower serum luteinising hormone levels (P < 0.005) than men living at sea level. At high altitude, the group with the highest CMS score (≥10) showed higher chronological age, SpO(2) , serum T and ratio T/E(2) than the group with CMS score of ≤4. Some symptoms of CMS as sleep disorders and paraesthesia were more related to high serum T level; cyanosis was more related to higher haemoglobin values. In conclusion, higher serum T levels were associated to higher scores of CMS.

Effect of the ethanolic extract from Fagara tessmannii on testicular function, sex reproductive organs and hormone level in adult male rats.

The effect of ethanolic extract of Fagara tessmannii, wide medicinal plants used on reproductive function in South Cameroon, was investigated in male rats. Twenty male sexually experienced rats (four groups) were orally treated with vehicle, 0.01, 0.1, 1 g kg(-1) BW per day of F. tessmannii (equivalent to 16.67 g, 33.33 g, 50 g, 66.66 g kg(-1) dry raw material) for 14 days, the upper limit dose without any clinical sign of toxicity was 2 g kg(-1). Fagara tessmannii extract negatively affected weight of accessory organs and significantly affected body weight gain at dose 1 g kg(-1) (P < 0.05) in treated rats. The weight of epididymis and seminal vesicle significantly decreased at low doses (0.01 g kg(-1)) while the prostate weight decreased at all doses (P < 0.05). The transit of spermatozoa in cauda epididymidis significantly increased at lower dose of 0.01 g kg(-1) (P < 0.05). In addition, F. tessmannii extract affected neither daily sperm production (DSP) and DSP per g nor sperm count in vas deferens and epididymis. The length of stages IX-I of the seminiferous tubule and serum testosterone level increased dose-dependently following 14 days of treatment (P < 0.05). The results suggest that F. tessmannii, 14 days after treatment, may improve spermatogenesis, testosterone level and sperm transit in cauda epididymidis but negatively impair reproductive organ activities.

Genetic Diversity and Host Range of Verticillium dahliae Isolates from Artichoke and Other Vegetable Crops in Spain.

Artichoke is severely affected by Verticillium wilt, caused by Verticillium dahliae, in eastern-central Spain, which is one of the most important vegetable-cropping areas in the country. To determine genetic and virulence variability in local populations of V. dahliae, 18 isolates collected from artichoke and other vegetable species cultivated in eastern-central Spain were selected to represent local vegetative compatibility groups (VCGs). Diversity in the isolates was characterized by molecular markers and virulence in 12 important hosts for that region. Recently developed microsatellite markers (simple-sequence repeats) and polymorphic sequences were used to assess the genetic variation among those isolates to reveal any association occurring among host source, VCG, and virulence. Although all isolates caused severe disease symptoms on artichoke, cardoon, eggplant, and watermelon, those from artichoke had a limited host range and isolates from watermelon, muskmelon, and eggplant were not pathogenic to some of the hosts tested. VCG diversity was related to differential virulence in certain hosts.

The process of truth disclosure: an assessment of the results of information during the diagnostic phase in patients with cancer.

BACKGROUND: Surveys carried out in Mediterranean countries demonstrated very low rates of awareness of both diagnosis and prognosis among cancer patients. In our institution, a long-term training program aimed at improving communication skills among all physicians interacting with cancer patients was conducted. We report here the results of an extensive assessment of patients' awareness conducted after the first training period. PATIENTS AND METHODS: In a 2-year period, after every first visit of patients with a histological diagnosis of cancer, oncologists elicited perception of the patients and completed a structured questionnaire focusing on the understanding of the diagnosis and prognosis. Our data are thus a photograph of the results of the informative process conducted during the diagnostic phase. RESULTS: Among the enrolled 649 patients, 79.3% were aware of their diagnosis; factors significantly associated with higher levels of awareness were age younger than 70 and referral from surgery (versus internal medicine). Knowledge about the palliative or curative aims of future treatments (a surrogate sign of prognostic consciousness) was evident in 55.2%. CONCLUSIONS: Compared with historical data, our results show a high level of comprehension of the diagnosis of malignancy, probably due to the extensive training effort together with the method chosen for assessment.

Antagonistic effect of Lepidium meyenii (red maca) on prostatic hyperplasia in adult mice.

The plants from the Lepidium gender have demonstrated to have effect on the size of the prostate. Lepidium meyenii (Maca) is a Peruvian plant that grows exclusively over 4000 m above sea level. The present study was designed to determine the effect of red maca (RM) in the prostate hyperplasia induced with testosterone enanthate (TE) in adult mice. Prostate hyperplasia was induced by administering TE, and then these animals (n = 6, each group) were treated with RM or Finasteride (positive control) for 21 days. There was an additional group without prostate hyperplasia (vehicle). Mice were killed on days 7, 14 and 21 after treatment with RM. Testosterone and oestradiol levels were measured on the last day of treatment. Prostatic stroma, epithelium and acini were measured histologically. RM reduced prostate weight at 21 days of treatment. Weights of seminal vesicles, testis and epididymis were not affected by RM treatment. The reduction in prostate size by RM was 1.59 times. Histological analysis showed that TE increased 2-fold the acinar area, effect prevented in the groups receiving TE + RM for 14 (P < 0.05) and 21 (P < 0.05) days and the group receiving TE + Finasteride for 21 days (P < 0.05). TE increased prostatic stroma area and this effect was prevented by treatment with RM since 7 days of treatment or Finasteride. The reduction in prostatic stroma area by RM was 1.42 times. RM has an anti-hyperplastic effect on the prostate of adult mice when hyperplasia was induced with TE acting first at prostatic stromal level.

Tropaeolum tuberosum (Mashua) reduces testicular function: effect of different treatment times.

Tropaeolum tuberosum Ruiz & Pavon, along with other several species, is an edible-tuber crop that grows in the Andean region. Folk medicine describes the use of mashua to reduce reproductive function in men. The present study aimed to evaluate the effect of mashua (1 g kg(-1)) on sperm production in rats during 7, 12, 21 and 42 days of treatment. The following parameters were assessed: reproductive organ weights, spermatid count and daily sperm production (DSP), sperm count in epididymis and sperm transit and serum testosterone levels. Freeze-dried extract of mashua had 3.7 g 100 g(-1) of benzyl glucosinolate. Mashua-treated rats showed a reduction in testicular spermatid number and DSP from day 12 to day 42; meanwhile, the effect of mashua was noted in epididymal sperm count after 12 and 42 days of treatment. In addition, epididymal sperm transit time was delayed at day 7 and it was accelerated on days 12 and 21 of treatment. No differences in serum testosterone levels were found between rats treated with vehicle and mashua after 42 days of treatment. Finally, mashua reduces testicular function after one spermatogenic cycle by reducing spermatid and sperm number, DSP and epididymal sperm transit time.

First Report of Fusarium Wilt of Coreopsis verticillata 'Moonbeam' Caused by Fusarium oxysporum in a Midwestern Nursery.

Disease symptoms were observed in a commercial nursery in the midwest on Coreopsis verticillata 'Moonbeam' during the summer of 2006. Plants in a roughly circular area in one field showed foliar necrosis, stem basal cankers, root rot, and eventually plant death. Vascular discoloration was noted in stems of affected plants. Sporulation typical of Fusarium oxysporum was observed on the surface of cankers. Five isolates of F. oxysporum (KR1, KR2, KR4, MDU, and MDL) were taxonomically identified from monosporic cultures obtained from surface-disinfested stems and roots. All five isolates were vegetatively compatible with each other. Two methods of inoculation were used. Method one (conidial drench) involved pouring 100 ml of conidial suspension (106 conidia per ml) into 10-cm pots containing one healthy 2-month-old division of the same cultivar that was obtained from a different nursery. Method two (millet infestation) involved mixing autoclaved millet seed that had been colonized by each isolate into potting mix (2.5 g/L of mix) prior to transplanting. Four plants were tested per isolate per method and controls received distilled water or autoclaved millet. After 3 months, only two isolates (KR1 and KR2) inoculated by conidial drench caused root rot, whereas all isolates inoculated by millet infestation caused wilt, root rot, and vascular discoloration, and all inoculated plants died after 3.5 months Controls remained healthy. The fungus was recovered and was vegetatively compatible with the original F. oxysporum isolates. The tef-α gene from two F. oxysporum isolates was sequenced, submitted to the Blast ID search at Pennsylvania State University (1), and found to belong to the F. oxysporum species complex. Two isolates (KR1 and KR 2) have been deposited at the Fusarium Research Center at Pennsylvania State University under deposition numbers O-2437 and O-2438. Because of the popularity of this coreopsis cultivar, this disease has the potential to cause significant economic loss in nurseries and landscape businesses. The affected nursery, however, has taken all precautions to avoid disseminating the pathogen. Reference: (1) D. M. Geiser et al. Eur. J. Plant Pathol. 110:473, 2004.

Utilidad de la telemedicina en la atención pediátrica urgente durante la pandemia por COVID-19 / Usefulness of telemedicine in urgent pediatric care during the COVID-19 pandemic

Introducción: nuestro sistema sanitario ha sufrido una reorganización sin precedentes priorizando la atención de los pacientes con sintomatología COVID-19. El uso de telemedicina se presenta como una alternativa útil en la era pos-COVID. El objetivo del estudio fue valorar la utilidad del servicio de mensajería de Twitter como herramienta de telemedicina para el cribado de patología urgente. Material y métodos: estudio descriptivo, retrospectivo y transversal de un programa de telemedicina desarrollado por un equipo de especialistas en Pediatría y sus Áreas Específicas durante el estado de alarma. Se recogieron datos demográficos, número y motivos de consultas según signos, síntomas y su forma de presentación (texto, foto o vídeo). Se analizó el número de consultas resueltas, derivaciones y el grado de satisfacción. Resultados: se atendió un total de 182 consultas realizadas en su mayoría por mujeres (71%), durante las primeras semanas del confinamiento (70%). El 100% fueron mensajes de texto, acompañados casi en un tercio de los casos de material audiovisual (27,2% fotos, 4,6% vídeos). La edad media de los pacientes atendidos fue de 2,72 ± 2,74 y los principales motivos de consulta: fiebre, exantemas y dificultad respiratoria. El 18,13% tuvo relación con la COVID-19, y solamente el 8,24% fue derivado. Conclusiones: aunque la telemedicina no puede reemplazar la valoración presencial y todavía existen limitaciones técnicas y legales, nuestros resultados sugieren que podría ser una alternativa prometedora para mejorar el acceso, reducir los tiempos de triaje, coordinar los recursos disponibles, y disminuir el riesgo de contagio y saturación de las instalaciones sanitarias (AU)

Introduction: our healthcare system has undergone an unprecedented reorganization, prioritizing the care of patients with COVID-19 symptoms. Telemedicine has emerged as a useful alternative in the post-COVID era. The aim of the study was to assess the usefulness of the Twitter® messaging service as a telemedicine tool for the screening of urgent pathology.Material and methods: cross-sectional, retrospective and descriptive study of a telemedicine programme developed by a team of specialists in paediatrics and its subspecialities during the state of alarm. We collected demographic data and the number and reasons for consultations based on the presenting signs and symptoms and how they were conveyed (text, photo and/or video). We analysed the number of resolved concerns, referrals and the degree of user satisfaction.Results: the service managed a total of 182 consultations, mostly made by women (71%) and during the first weeks of the survey (70%). All consultations included text, accompanied in almost 1/3 of the cases by audiovisual content (27.2% photo, 4.6% video). The average age of the managed patients was 2.72 ± 2.74 years and the main reasons for consultation were fever, exanthema and respiratory difficulty. Of all consultations, 18.13% were related to COVID-19, and only 8.24% led to referral.Conclusions: although telemedicine cannot replace face-to-face assessment and there are still technical and legal limitations, our results suggest that it could be a promising alternative to improve access, reduce triage times, coordinate available resources, and decrease the risk of contagion and the saturation of health care facilities. (AU)

Preferential retention of codon 72 arginine p53 in squamous cell carcinomas of the vulva occurs in cancers positive and negative for human papillomavirus.

We have sought to determine the basis for preferential loss of the codon 72 proline (72P) rather than the arginine (72R) allele in squamous cell carcinoma of the vulva with loss of heterozygosity (LOH) in p53. The proportion of cases containing human papillomavirus (HPV) 16 was not statistically different among individuals with either 72RR or 72RP in the germ line (P > 0.99), but p53 LOH was significantly more common in individuals heterozygous 72RP than in 72RR individuals (P = 0.04). LOH more commonly involved the 72P allele in both HPV-positive and HPV-negative cancers. Our results imply that preferential loss of the 72P allele in vulval squamous cell carcinoma occurs by HPV-dependent and -independent mechanisms.

Radioimmunoguided surgery after primary treatment of locally advanced breast cancer.

PURPOSE: To assess the role of radioimmunoguided surgery (RIGS) using a handheld intraoperative gamma-detecting probe (GDP) to identify neoplastic disease after primary chemotherapy in locally advanced breast cancer (LABC) patients injected with iodine 125-labeled monoclonal antibodies (MAbs). PATIENTS AND METHODS: Twenty-one patients with histologically documented LABC were treated with a combined modality approach. After three courses of primary chemotherapy and before modified radical mastectomy, the 125I-radiolabeled MAbs B72.3 (anti-TAG72) and FO23C5 (anti-carcinoembryonic antigen [CEA]) were administered to 11 patients (group A) and 10 patients (group B), respectively. At surgery, a GDP was used to locate the primary tumor and to assess possible tumor multicentricity and the presence of ipsilateral axillary metastases. Routine pathologic examination was performed in neoplastic and normal tissue specimens of all 21 patients. In addition, immunohistochemical assay for TAG72 and CEA expression was performed. RESULTS: In group A patients, RIGS identified primary tumor in seven of 11 patients (63.3%) and unpalpable multicentric tumor lesions were located in two of four (50%). Positive axillary lymph nodes were histologically documented in eight of 11 patients (72.7%) and RIGS identified three of eight (37.5%). In group B, RIGS located the primary tumor lesion in four of 10 patients (40%); in two cases, the tumor was not clinically evident. Multicentricity was observed in one of two patients and lymph node involvement in three of nine (33.3%). No false-positive results were observed in either group A or B. CONCLUSION: RIGS appears to be a safe and reliable technique. However, the MAbs used in this study are not sufficiently specific. RIGS represents a technique for which the full potential for intraoperative assessment of breast cancer lesions can be reached when more specific antibodies become readily available.

In vitro effects of cholesteryl butyrate solid lipid nanospheres as a butyric acid pro-drug on melanoma cells: evaluation of antiproliferative activity and apoptosis induction.

Literature data show that butyric acid derivatives bear a dose-dependent differentiative anti-proliferative activity on cancer cell lines and that apoptosis induction may play a major role. Although it was recently shown that solid lipid nanospheres (SLNs) are a suitable tool for several in vivo drug administration routes, there is little available information on melanoma cell lines. This study was aimed at evaluating the anti-proliferative and apoptotic in vitro effects of cholesteryl butyrate (chol-but) SLNs on melanoma cells. Increasing concentrations of chol-but SLNs were used to test two melanoma cell lines. Both cell lines were treated with Na-butyrate (Na-but) and chol-but SLNs for viability. Those tested with chol-but SLNs were more effective than Na-butirate (3 to 72 h). The apoptotic effects of chol-but SLNs were evaluated between 3 and 72 h by annexin-V (ANX-V)/propidium iodide (PI) staining and the antiproliferative effect by PI staining. Apoptosis anti-proliferative-regulatory proteins as bcl-2, Fas/APO1 (CD95) and PCNA (PC10) were also investigated. Flow cytometric analyses evidenced a G(0/1)-S transition block and a 'sub-G(0/1)' apoptotic peak from 0.5 to 1.0 mM butyric acid. In ANX-V/PI flow cytometric staining, a dose- and time-dependent increase in the apoptotic cell percentage (ANX-V+) coupled with a down-regulation of PC10 and bcl-2 and a parallel up-regulation of Fas/APO1 (CD95) were found in both lines started after 3 to 24 h of chol-but SLNs treatment. Results show that chol-but SLNs exerts a dose/time-dependent effect in melanoma cell apoptosis induction between 3 and 24 h and a dose but not time-dependent effect after 24 h of treatment.

Effect of Lepidium meyenii (Maca) on spermatogenesis in male rats acutely exposed to high altitude (4340 m).

Lepidium meyenii (Maca) is a Peruvian hypocotyl that grows exclusively between 4000 and 4500 m in the central Andes. Maca is traditionally employed in the Andean region for its supposed fertility-enhancing properties. The aim of this study was to test the hypothesis that Maca can prevent high altitude-induced testicular disturbances. Adult male rats were exposed for 21 days to an altitude of 4340 m and treated with vehicle or aqueous extract of Maca (666.6 mg/day). The lengths of the stages of the seminiferous epithelium and epididymal sperm counts were obtained at 0, 7, 14 and 21 days of exposure. The stages of the seminiferous tubules were assessed by transillumination. A dose-response study was also performed at sea level to determine the effect of Maca given to male rats at doses of 0, 6.6, 66.6 and 666.6 mg/day for 7 days on body weight, seminiferous tubule stages and epididymal sperm count. The length of stage VIII and the epididymal sperm count were increased in a dose-dependent manner in Maca-treated rats but treatment reduced the length of stage I. At the highest dose, sperm count increased 1.58 times, the length of stage VIII increased 2.4 times and the length of stage I was reduced 0.48 times compared with the value at dose 0. Exposure to high altitude resulted in a reduction in epididymal sperm count after 7 days and lower values were maintained up to 21 days. Altitude reduced spermiation (stage VIII) to half and the onset of spermatogenesis (stages IX-XI) to a quarter on days 7 and 14 but treatment with Maca (666.6 mg/day) prevented these changes. Data on transillumination and epididymal sperm count in the Maca-treated group exposed to high altitude were similar to those obtained at sea level. Maca increased the sperm count on day 21 of exposure to high altitude to values similar (1095.25 +/- 20.41x10(6) sperm, means +/- S.E.M.) to those obtained in the Maca-treated group at sea level (1132.30 +/- 172.95x10(6) sperm). Furthermore, in the Maca-treated group exposed for 21 days to high altitude, epididymal sperm count was higher than in the non-treated group at sea level (690.49 +/- 43.67x10(6) sperm). In conclusion, treatment of rats with Maca at high altitude prevented high altitude-induced spermatogenic disruption.

Vinorelbine as palliative therapy in advanced breast cancer.

Thirty advanced breast cancer patients received Vinorelbine (VNB) according to two different schedules: a weekly i.v. bolus of 30 mg/m (14 patients) or a continuous infusion (CI) schedule comprising 8 mg i.v. bolus on day 1 followed by 8 mg/m2/die CI day 1 to 4, q 21 days (16 patients). 36% of patients had received at least two prior chemotherapy regimens for advanced disease and 57% had been treated with anthracycline-based palliative therapy. The overall response rate (CR + PR) was 33% (soft tissue 57%, bone 17%, viscera 29%). The main toxicities were neutropenia and abdominal pain. Vinorelbine is effective in pretreated advanced breast cancer patients.