Histopathological insights into hair loss in Cronkhite-Canada syndrome: diffuse anagen-telogen conversion precedes clinical hair loss progression.

Cronkhite-Canada syndrome (CCS) is a rare disorder characterised by gastrointestinal polyposis and ectodermal changes, represented by extensive alopecia. Detailed histopathological investigations of alopecic lesions in two female CCS patients with severe hair loss revealed a marked increase in telogen hair follicles with no sign of loss or of the minaturisation or atrophy of hair follicle structures and the absence of inflammatory change, despite severe inflammation in the gastrointestinal tract. These findings suggested that hair regrowth can be expected without systemic corticosteroids, if they are not necessary for treatment of the gastrointestinal tract, and that anagen-telogen transition is an early event preceding clinical hair loss in CCS.

A severe course of Cronkhite-Canada syndrome and the review of clinical features and therapy in 49 Chinese patients.

We describe a severe case of Cronkhite-Canada syndrome and review the clinical features and therapy in 49 Chinese patients. A 67-year-old man who underwent severe chronic diarrhea had typical clinical manifestations of hyperpigmentation, hair loss, and dystrophic changes in the fingernails. Although sufficient nutrition support and other therapies reported in the literature were provided, the patient died of systemic failure one year later. Cronkhite-Canada syndrome is characterized by generalized gastrointestinal polyps associated with hyperpigmentation, hair loss, and onycholysis. Anemia, positive stool occult blood, serum electrolyte disturbances, and low serum proteins are the main clinical features of patients with Cronkhite-Canada syndrome. Most patients were diagnosed by esophagogastroduodenoscopy and/or colonoscopy, and polyps were found in the entire alimentary tract, except the notable exception of the esophagus. The polyp-like samples of mucosa, hyperplasia, and adenoma were characterized by acute/chronic inflammation. Four cases were complicated with cancer. The treatment of Cronkhite-Canada syndrome includes symptomatic and support therapy, administration of corticosteroids, antibiotics and acid inhibitors, therapeutic endoscopy, and surgery. While the mortality rate was reported as 47.3% (9/19), some patients may live a long life with controlled symptoms.

Dose-dependent suppression of hyperlipidemia and intestinal polyp formation in Min mice by pioglitazone, a PPAR gamma ligand.

In our previous study, a peroxisome proliferator-activated receptor gamma (PPAR gamma) agonist, pioglitazone, suppressed both hyperlipidemia and intestinal polyp formation in Apc(1309) mice at doses of 100 and 200 ppm in the diet. In contrast, it has been reported that doses of 1500 or 2000 ppm of another PPAR gamma agonist, troglitazone, enhanced colon polyp development in Min mice. In the present study, we therefore investigated the effects of a wide range of pioglitazone doses on both hyperlipidemia and intestinal polyp formation in Min mice. Serum triglycerides and very low density lipoprotein (VLDL) cholesterol in the basal diet group were elevated to levels 13-15 times higher than those in the wild-type counterparts at 20 weeks of age. They were reduced dose-dependently by treatment with 100, 200, 400 and 1600 ppm pioglitazone from 6-20 weeks of age with suppression to almost the wild-type level at the highest dose. Moreover, up-regulation of the liver mRNA levels for lipoprotein lipase (LPL) was evident in the pioglitazone-treated animals. Dose-dependent reduction of intestinal polyps was observed in Min mice given 100-1600 ppm for 14 weeks, total numbers being decreased to 63-9% of the control value. A suppressive effect of pioglitazone on colon polyp formation was also found. The PPAR gamma agonist, pioglitazone, may thus be a promising candidate chemopreventive agent for colon cancer.

Concomitant suppression of hyperlipidemia and intestinal polyp formation in Apc-deficient mice by peroxisome proliferator-activated receptor ligands.

Epidemiological studies have shown a positive association of colon cancer with hyperlipidemia. Furthermore, signaling generated by peroxisome proliferator-activated receptor (PPAR) alpha and gamma ligands, suggested to be candidate tumor preventive agents, has been shown to lower serum triglyceride levels. In the present study, we assessed hyperlipidemia in Apc-deficient mice, model animals for human familial adenomatous polyposis, and examined the effects of pioglitazone and bezafibrate, respectively, PPARgamma and PPARalpha agonists, on both hyperlipidemia and intestinal polyposis. Serum lipid levels in Apc(1309) mice and Min mice from 6 to 15 weeks of age were measured. Although serum levels of triglyceride and cholesterol were low in both Apc(1309) and wild-type mice at 6 weeks, triglycerides were elevated 10-fold in Apc(1309) mice by the age of 12 weeks but not in their wild-type counterparts. Cholesterol was also increased significantly, and marked centrilobular-restricted steatosis was observed in the livers of aged Apc(1309) mice. Similar findings were observed for Min mice at 15 weeks of age. Moreover, lipoprotein lipase mRNA levels in the liver and small intestine of Apc(1309) and Min mice were demonstrated to be lower than those in wild-type mice. Treatment of Apc(1309) mice with 100 and 200 ppm pioglitazone or bezafibrate for 6 weeks from 6 weeks of age caused dose-dependent reduction in serum triglycerides and cholesterol, along with reduction in the numbers of intestinal polyps to 67% of the control value. The present study clearly demonstrated a hyperlipidemic state in Apc gene-deficient mice and a potential of PPARalpha and PPARgamma ligands to suppress both hyperlipidemia and polyp formation. Hyperlipidemia in these mice may thus be associated with their intestinal lesion development.