The Effects of an Osteoarthritic Joint Environment on ACL Damage and Degeneration: A Yucatan Miniature Pig Model.

Posttraumatic osteoarthritis (PTOA) arises secondary to joint injuries and is characteristically driven by inflammatory mediators. PTOA is often studied in the setting of ACL tears. However, a wide range of other injuries also lead to PTOA pathogenesis. The purpose of this study was to characterize the morphological changes in the uninjured ACL in a PTOA inflammatory environment. We retrospectively reviewed 14 ACLs from 13 Yucatan minipigs, 7 of which had undergone our modified intra-articular drilling (mIAD) procedure, which induced PTOA through inflammatory mediators. Seven ACLs were harvested from mIAD minipigs (PTOA) and seven ACLs from control minipigs with no cartilage degeneration (non-PTOA). ACL degeneration was evaluated using histological scoring systems. IL-1ß, NF-κB, and TNF-α mRNA expression in the synovium was measured using qRT-PCR. PTOA minipigs demonstrated significant ACL degeneration, marked by a disorganized extracellular matrix, increased vascularity, and changes in cellular shape, density, and alignment. Furthermore, IL-1ß, NF-κB, and TNF-α expression was elevated in the synovium of PTOA minipigs. These findings demonstrate the potential for ACL degeneration in a PTOA environment and emphasize the need for anti-inflammatory disease-modifying therapies following joint injury.

Lack of progressive hepatic fibrosis during long-term therapy with deferiprone in subjects with transfusion-dependent beta-thalassemia.

Patients with thalassemia major require lifelong chelation therapy to prevent iron-induced organ damage. The orally active chelator deferiprone has been proposed as an alternative for patients unable or unwilling to use deferoxamine. One report has concluded that deferiprone may worsen hepatic fibrosis in patients with thalassemia, whereas others have found no detrimental effect. A panel of 3 pathologists evaluated 112 coded liver biopsies obtained from 56 patients before and after deferiprone therapy. Fibrosis was scored with the Laennec and Ishak systems. The mean interval between liver biopsies was 3.1 years (range, 1.2-4.9 years). In 11 patients seronegative for hepatitis C, fibrosis scores before and after therapy were 1.12 +/- 1.07 and 0.97 +/- 0.84 (P =.42) with the use of the Ishak system, and 0.71 +/- 0.65 and 0.70 +/- 0.53 (P =.91) with the Laennec system. Among 45 patients seropositive for hepatitis C, fibrosis scores before and after therapy were 1.91 +/- 1.13 and 2.04 +/- 1.30 (P =.43) with the use of the Ishak system and 1.26 +/- 0.73 and 1.35 +/- 0.90 (P =.41) with the Laennec system. When the data set was limited to biopsies that each contained 6 or more portal tracts (31 patients), analysis still showed no significant change in fibrosis with time. With the use of the Laennec system, the fibrosis score did not increase by more than one level in any patients without hepatitis C; it increased by more than one level in 1 patient with hepatitis C; and it did not decrease by more than one level in any of the 56 patients. This analysis of the largest collection of liver biopsies reported to date in patients receiving deferiprone demonstrates no evidence of deferiprone-induced progression of hepatic fibrosis during long-term therapy.

Variations in globin chain synthesis in hereditary persistence of fetal haemoglobin

Globin synthesis was studied in four Negro families including 10 members with Hb A-HPFH and four with Hb S-HPFH. The á/O specific activity ratios in 10 of these patients with Hb A-HPFH heterozygotes were similar to those of the control group. In two patients with Hb A-HPFH, the á/O ratio was slightly decreased in one (0.84) and clearly decreased in another (0.78). In two of the patients with Hb S-HPFH the ratios were clearly decreased (0.71 and 0.75). The extended range of á/O ratios in these 14 patients is similar to that of Negro patients with á-thalassaemia trait. These studies indicate that a decreased á/O ratio may be found in HPFH, as well as in á-thalassaemia. Bone marrow globin synthesis was measured in two patients with Hb S-HPFH and decreased peripheral blood á/O ratios, and in one with Hb A-HPFH and a normal peripheral blood á/O ratio. In each patient the (á+y)/O ratio of radioactivities as well as the á/O specific activity ratio was close to I and therefore balanced, indicating more rapid decay of á-chain synthesis relative to O-chain during red cell maturation or extremely rapid destruction of newly synthesized excess O-chains in the bone marrow.(Summary)

Globin synthesis in the Jamaican Negro with beta-thalassemia

Globin synthesis was studied in three Jamaican Negro families with 18 heterozygotes and 5 homozygotes for beta-thalassemia. Synthesis of the beta chain of Hb A in the peripheral blood of heterozygotes was equal to that of the alpha-chain in 10 patients and was decreased in the remainder. In one patient with Hb C beta-thalassemia the beta/alpha ratio was normal. These findings were similar to those in American Negroes, but differed from those in Caucasian with beta-thalassemia trait, in each of whom the beta/alpha ratio was decreased. Globin synthesis was balanced in the bone marrows of Negro and Caucasian heterozygotes. Despite the milder clinical disease in Negro homozygotes as compared to Caucasian patients, the beta/alpha ratios were similar in both groups. The presence of alpha-thalassemia combined with beta-thalassemia in Negro heterozygotes is not a likely explanation for the high incidence of balanced globin synthesis ratios. The expression of relative beta to alpha chain synthesis in Negro heterozygotes appears to be modified by a factor which is not linked to the delta-chain locus. The nature of this factor is not known at present.(Summary)