Plitidepsin to treat multiple myeloma.

While remaining relatively rare, multiple myeloma (MM) accounts for approximately 10% of all hematological malignancies, being an insidious disease with an overall 5-year survival rate of 52%. In addition to other associated complications, myeloma bone disease further aggravates MM patients, the majority of whom suffer from lytic lesions, leading to pain, fractures, mobility issues and neurological deficits. Patients not responding or becoming resistant to prior therapies have now a novel therapeutic tool with an unprecedent mode of action, differing from those currently in use. The anticancer effects of the marine-derived antitumor agent plitidepsin primarily rely on the interaction with elongation factor 1-α 2 (eEF1A2), known to be overexpressed in breast cancer and MM cells, targeting the noncanonical role of the protein and leading to a proapoptotic response. Following the drug's approval from Australian regulatory authorities, eligible patients will have access to a new first-in-class drug to treat MM, expanding the current anti-MM portfolio. Plitidepsin (Aplidin; PharmaMar) was approved in combination with the corticosteroid agent dexamethasone, to treat MM patients who failed or became resistant to other therapies, covering the third- and fourth-line treatment setting.

High temperature AFM study of CAP 30/45 pen grade bitumen.

Bitumen is a complex mixture of hydrocarbons for which microstructural understanding is incomplete. In an effort to detail this microstructure, a asphalt cement sample (CAP 30/45) was analysed by thermal phase detection atomic force microscopy. Phase contrast and topography images showed that sample morphology is highly dependent on temperature. The 'bee structure' changed considerably at temperatures between 50 degrees C and 56 degrees C. A decrease of the oscillation amplitude was observed upon heating and the 'bees' completely disappeared at temperatures above 57 degrees C. When the temperature was decreased after melting at 170 degrees C, the 'bees' began to nucleate gradually at temperatures of 57 degrees C and its evolution with time was followed. Changes in morphology were compared to thermal analysis results and a model for the 'bee' structure was proposed.

Oral rapamycin attenuates atherosclerosis without affecting the arterial responsiveness of resistance vessels in apolipoprotein E-deficient mice

The objective of the present study was to assess the effects of the immunosuppressant rapamycin (Rapamune®, Sirolimus) on both resistance vessel responsiveness and atherosclerosis in apolipoprotein E-deficient 8-week-old male mice fed a normal rodent diet. Norepinephrine (NE)-induced vasoconstriction, acetylcholine (ACh)- and sodium nitroprusside (SNP)-induced vasorelaxation of isolated mesenteric bed, and atherosclerotic lesions were evaluated. After 12 weeks of orally administered rapamycin (5 mg·kg-1·day-1, N = 9) and compared with untreated (control, N = 9) animals, rapamycin treatment did not modify either NE-induced vasoconstriction (maximal response: 114 ± 4 vs 124 ± 10 mmHg, respectively) or ACh- (maximal response: 51 ± 8 vs 53 ± 5 percent, respectively) and SNP-induced vasorelaxation (maximal response: 73 ± 6 vs 74 ± 6 percent, respectively) of the isolated vascular mesenteric bed. Despite increased total cholesterol in treated mice (982 ± 59 vs 722 ± 49 mg/dL, P < 0.01), lipid deposition on the aorta wall vessel was significantly less in rapamycin-treated animals (37 ± 12 vs 68 ± 8 µm² x 10³). These results indicate that orally administered rapamycin is effective in attenuating the progression of atherosclerotic plaque without affecting the responsiveness of resistance vessels, supporting the idea that this immunosuppressant agent might be of potential benefit against atherosclerosis in patients undergoing therapy.

Oral rapamycin attenuates atherosclerosis without affecting the arterial responsiveness of resistance vessels in apolipoprotein E-deficient mice.

The objective of the present study was to assess the effects of the immunosuppressant rapamycin (Rapamune, Sirolimus) on both resistance vessel responsiveness and atherosclerosis in apolipoprotein E-deficient 8-week-old male mice fed a normal rodent diet. Norepinephrine (NE)-induced vasoconstriction, acetylcholine (ACh)- and sodium nitroprusside (SNP)-induced vasorelaxation of isolated mesenteric bed, and atherosclerotic lesions were evaluated. After 12 weeks of orally administered rapamycin (5 mg.kg-1.day-1, N = 9) and compared with untreated (control, N = 9) animals, rapamycin treatment did not modify either NE-induced vasoconstriction (maximal response: 114 +/- 4 vs 124 +/- 10 mmHg, respectively) or ACh- (maximal response: 51 +/- 8 vs 53 +/- 5%, respectively) and SNP-induced vasorelaxation (maximal response: 73 +/- 6 vs 74 +/- 6%, respectively) of the isolated vascular mesenteric bed. Despite increased total cholesterol in treated mice (982 +/- 59 vs 722 +/- 49 mg/dL, P < 0.01), lipid deposition on the aorta wall vessel was significantly less in rapamycin-treated animals (37 +/- 12 vs 68 +/- 8 microm(2) x 10(3)). These results indicate that orally administered rapamycin is effective in attenuating the progression of atherosclerotic plaque without affecting the responsiveness of resistance vessels, supporting the idea that this immunosuppressant agent might be of potential benefit against atherosclerosis in patients undergoing therapy.

Population health needs beyond ratifying the Kyoto Protocol: a look at occupational deprivation.

The dramatic impact of climate change is physically and economically affecting the world, a consequence of neglecting scientific information known since the 1960s and 1970s. International discussion has focused on the needs of the physical environment and general health concerns (such addressing greenhouse gas production and population health issues); however, little acknowledgement has yet been made of local human issues, such as the effect of climate change on the mental health of those in rural communities. This commentary takes an occupational science perspective to describe new ways of classifying potential mental health problems associated with climate change and its impact on the rural environment. It challenges policy makers to take a proactive approach to addressing the current impacts of climate change on the future mental health of individuals in rural communities.

Follow-up of kidney donors who developed uremia and went on the waiting list for a transplant: should they have allocation priority?

BACKGROUND: The increasing use of living kidney donors requires knowledge about long-term effects, especially number and causes of donors with chronic renal failure (CRF), and discussion about a regular follow-up program for donors, policies giving priority to kidney donors on the waiting list for a kidney, and a national record of donors. METHODS: We performed a Retrospective analysis of 470 records of our kidney donors from the kidney transplantation unit between 1977 and 1997. RESULTS: Five out of the 470 donors developed CRF (1.1%), with a calculated incidence of 610 per million people a year. CONCLUSION: The data showed that the risk of a donor developing CRF may be higher than in the in general population. These results showed the necessity of creating an effective follow-up program for donors and a national record.

Availability of over-the-counter drugs for arthritis in Sao Paulo, Brazil.

Seventy pharmacies located in Sao Paulo were randomly selected and visited. Seven researchers posed as ordinary clients presenting with a standardized complaint of symptoms according to a scenario previously defined. The client asked for medicines to relieve his/her pain or discomfort. After the seller's suggestion the client asked for 2 drugs randomly selected from a drug list containing 30 trademarked drugs commonly prescribed to arthritis patients. These drugs should be available only on prescription. In only 12.8% of the pharmacies did the seller initially suggest the client see a physician. The sellers "prescribed' non-steroid anti-inflammatory drugs (NSAID), vitamins, analgesics (AN) and corticosteroids (CO) in respectively 42.8, 20.0, 14.3 and 5.7% of the visits. From the drug list, the client secured 67.7% of the NSAID, 65.0% of the CO and 20.0% of the sedatives without presenting a prescription. Pharmacy sellers usually comply with the clients demands. Future studies should aim at the evaluation of interventions to reduce the availability of the over-the-counter drugs for arthritis.

Juvenile dermatomyositis and pregnancy: report and literature review.

Reports of dermatomyositis (DM) and polymyositis complicating pregnancy are rare. Only nineteen cases have been published. We describe the first case in which juvenile DM appeared during pregnancy. An emergency cesarean section had to be performed due to fetal distress at 37 weeks of gestation. Patient and infant are doing well after 8 months of followup.

The effectiveness of tipi in the treatment of hip and knee osteoarthritis--a preliminary report.

Osteoarthritis (OA) is a common painful inflammatory condition occurring mainly in the later half of life. Hip and knee are the joints mostly affected. Petiveria alliacea (tipi) popularly known as an anti-rheumatic medicine, has been used by OA patients to relief pain. This one-week cross-over double-blind trial has preliminary evaluated the analgesic effect of tipi tea in 14 patients with hip and knee OA. Imperata exaltata (sape) was used as the Placebo tea. The pain assessments that were made at baseline and before the start of the second treatment period by treatment groups were comparable. While taking tipi or placebo tea patients experienced a statistically significant improvement in pain on motion and pain at night. The comparison between the improvements reported while on tipi and placebo tea, however, did not disclose any statistically significant difference. At the conclusion of the study 7 patients preferred tipi tea and 6 preferred placebo tea (NS). Two patients reported insomnia, one during placebo treatment and the other during tipi treatment.