The role of cytokines in postmenopausal osteoporosis.

Postmenopausal osteoporosis is a silent systemic progressive disease characterised by a decrease in bone mass per unit volume. This condition compromises the physical strength of the skeleton and increases the susceptibility to fractures on minor trauma. The imbalance between bone formation and bone resorption is known to be responsible for postmenopausal bone loss. Estrogen deficiency contributes to bone loss by increasing the production of pro-inflammatory cytokines by bone marrow and bone cells. Clinical and molecular evidence indicates that estrogen-regulated cytokines exert regulatory effects on bone turnover implicating their role as being the primary mediators of the accelerated bone loss at menopause. The current perspective on the role and interaction of cytokines such as IL-1, IL-4, IL-6, IL-17, TNF, IFN-γ and TGF-ß in bone loss linked with estrogen deficiency is reviewed. Current treatment options and emerging drug therapies in the management of postmenopausal osteoporosis are also evaluated.

The role of cytokines in skin aging.

Cutaneous aging is one of the major noticeable menopausal complications that most women want to fight in their quest for an eternally youthful skin appearance. It may contribute to some maladies that occur in aging which, despite not being life-threatening, affect the well-being, psychological state and quality of life of aged women. Skin aging is mainly affected by three factors: chronological aging, decreased levels of estrogen after menopause, and environmental factors. Aged skin is characterized by a decrease in collagen content and skin thickness which result in dry, wrinkled skin that is easily bruised and takes a longer time to heal. Cytokines play a crucial role in the manifestation of these features of old skin. The pro-inflammatory cytokine tumor necrosis factor-alpha inhibits collagen synthesis and enhances collagen degradation by increasing the production of MMP-9. It also lowers the skin immunity and thus increases the risk of cutaneous infections in old age. Deranged levels of several interleukins and interferons also affect the aging process. The high level of CCN1 protein in aged skin gives dermal fibroblasts an 'age-associated secretory phenotype' that causes abnormal homeostasis of skin collagen and leads to the loss of the function and integrity of skin. Further research is required especially to establish the role of cytokines in the treatment of cutaneous aging.

The role of cytokines in cardiovascular disease in menopause.

Various studies suggest that increased levels of pro-inflammatory cytokines play a key role in the declining ovarian function and the resulting complications associated with menopause. In this review article, the authors outline the role of pro- and anti-inflammatory cytokines in cardiovascular disease during menopause.

Phase II study of single-agent bosutinib, a Src/Abl tyrosine kinase inhibitor, in patients with locally advanced or metastatic breast cancer pretreated with chemotherapy.

BACKGROUND: This phase II study evaluated single-agent bosutinib in pretreated patients with locally advanced or metastatic breast cancer. PATIENTS AND METHODS: Patients received oral bosutinib 400 mg/day. The primary end point was the progression-free survival (PFS) rate at 16 weeks. Secondary end points included objective response rate, clinical benefit rate, 2-year overall survival rate, safety, and changes in levels of bone resorption/formation biomarkers. RESULTS: Seventy-three patients were enrolled and treated. Median time from diagnosis of metastatic disease to initiation of bosutinib treatment was 24.5 months. For the intent-to-treat population, the PFS rate at 16 weeks was 39.6%. Unexpectedly, all responding patients (n = 4) were hormone receptor positive. The clinical benefit rate was 27.4%. The 2-year overall survival rate was 26.4%. The main toxic effects were diarrhea (66%), nausea (55%), and vomiting (47%). Grade 3-4 laboratory aminotransferase elevations occurred in 14 (19%) patients. Myelosuppression was minimal. No consistent changes in the levels of bone resorption/formation biomarkers were seen. CONCLUSIONS: Bosutinib showed promising efficacy in prolonging time to progression in chemotherapy-pretreated patients with locally advanced or metastatic breast cancer. Bosutinib was generally well tolerated, with a safety profile different from that of the Src/Abl tyrosine kinase inhibitor dasatinib in a similar patient population.

Unusual infections following allogeneic bone marrow transplantation for chronic lymphocytic leukemia.

Unusually severe infections phenomena were observed in three patients with chronic lymphocytic leukemia (CLL) who had undergone allogeneic bone marrow transplantation (BMT) from matched sibling donors. The first developed three episodes of cytomegaloviremia requiring anti-viral therapy; the third episode accompanied by cytomegalovirus hepatitis which required prolonged therapy with foscarnet. Another had Listeria monocytogenes meningitis which was difficult to eradicate and required prolonged maintenance antimicrobial therapy with oral trimethoprim-sulfamethoxazole and intrathecal gentamicin until death due to chronic graft-versus-host disease. The third patient had cytomegaloviremia lasting 47 days, which did not clear within 4 weeks of full-dose ganciclovir. Although the number of patients is small, in our experience the problems encountered were unusually severe compared with patients allografted for other disease. We conclude that CLL patients undergoing allogeneic BMT may be at a higher risk of infectious complications than patients allografted for other diseases, and require careful monitoring.

Partial relapse of Bell's palsy following superficial radiotherapy to a basal cell carcinoma in the temple.

A patient who developed a partial relapse of Bell's palsy following superficial radiotherapy to a basal cell carcinoma in the temple is reported. Nerves injured by Bell's palsy may be more susceptible to radiation induced damage.

Natural progesterone and antihypertensive action.

In a placebo controlled, double blind crossover study natural progesterone was given by mouth, in increasing doses, to six men and four postmenopausal women with mild to moderate hypertension who were not receiving any other antihypertensive drugs. When compared with values recorded before treatment and during administration of placebo progesterone caused a significant reduction in blood pressure, suggesting that progesterone has an antihypertensive action rather than a hypertensive one as has been previously thought. This possible protective effect of progesterone should be investigated further.