Cyclodextrin-mediated enhancement of riboflavin solubility and corneal permeability

Cyclodextrins are water-soluble cyclic oligosaccharides consisting of six, seven, and eight α-(1,4)-linked glucopyranose subunits. This study reports the use of different cyclodextrins in eye drop formulations to improve the aqueous solubility and corneal permeability of riboflavin. Riboflavin is a poorly soluble drug with a solubility up to 0.08 mg mL–1 in deionized water. It is used as a drug topically administered to the eye to mediate UV-induced corneal cross-linking in the treatment of keratoconus. Aqueous solutions of β-cyclodextrin (10–30 mg mL–1) can enhance the solubility of riboflavin up to 0.12–0.19 mg mL–1, whereas the higher concentration of α-cyclodextrin (100 mg mL–1) achieved a lower level of enhancement of 0.11 mg mL–1. The other oligosaccharides were found to be inefficient for this purpose. In vitro diffusion experiments performed with fresh and cryopreserved bovine cornea have demonstrated that β-cyclodextrin enhances riboflavin permeability. The mechanism of this enhancement was examined through microscopic histological analysis of the cornea and is discussed in this paper

Pulmonary hyalinizing granuloma: a multicenter study of 5 new cases and review of the 135 cases of the literature

International audiencePulmonary hyalinizing granuloma (PHG) is a rare disease characterized by single or multiple benign lung nodules mimicking lung neoplasma. Histologic analysis reveals homogenous hyaline lamellae, usually surrounded by collection of plasma cells, lymphocytes and histiocytes in a perivascular distribution. The clinical and radiological findings have been described in small series, but the long-term outcomes have rarely been reported. The objectives were to describe the clinical, radiological and outcomes of PHG in new cases and through a literature review. Patients with PHG were found by a multicenter search among French departments of internal medicine, pulmonology and anatomo-pathology. Review of the literature was made through the National Library of Medicine’s MEDLINE database using keywords “hyalinizing granuloma.” Five news cases and 135 cases of the literature were found. There were 82 men and 57 women, mean age at the diagnosis 44.6 years (15–83). Patients were frequently asymptomatic (n = 39, 27.4 %). The nodule was unique in 37 cases (28.9 %) and multiple in 91 cases (71.1 %). 18FDG PET scan revealed hypermetabolism of the nodule in 9/15 cases (60 %). A systemic disease was associated in 65 cases (mainly mediastinal and retroperitoneal fibrosis, autoimmune, tumoral or infectious disease or thromboembolism). The outcomes were evaluated in 73 patients when follow-up was available: 14 patients had a surgical resection of the nodule. Forty-five patients did not receive any immunosuppressive drug. Among these patients, 2 improved, 29 were stable and 14 worsened. Corticosteroids were used as a monotherapy in 19 patients and led to radiological improvement in 8 cases, stabilization in 8 cases and worsening in 3 cases. Five patients were treated with corticosteroids and at least one immunosuppressive drug and 4 patients improved. PHG is a rare benign disease, mimicking lung neoplasma, frequently associated with systemic diseases

The role of the intestine in the pathophysiology and management of severe acute pancreatitis

BackgroundThe outcome of severe acute pancreatitis has scarcely improved in 10 years. Further impact will require new paradigms in pathophysiology and treatment. There is accumulating evidence to support the concept that the intestine has a key role in the pathophysiology of severe acute pancreatitis which goes beyond the notion of secondary pancreatic infection. Intestinal ischaemia and reperfusion and barrier failure are implicated in the development of multiple organ failure.DiscussionConventional management of severe acute pancreatitis has tended to ignore the intestine. More recent attempts to rectify this problem have included 1) resuscitation aimed at restoring intestinal blood flow through the use of appropriate fluids and splanchnic‐sparing vasoconstrictors or inotropes; 2) enteral nutrition to help maintain the integrity of the intestinal barrier; 3) selective gut decontamination and prophylactic antibiotics to reduce bacterial translocation and secondary infection. Novel therapies are being developed to limit intestinal injury, and these include antioxidants and anti‐cytokine agents. This paper focuses on the role of the intestine in the pathogenesis of severe acute pancreatitis and reviews the implications for management