Non-operative management of shoulder osteoarthritis: Current concepts.

Glenohumeral osteoarthritis (OA) is one of the most common causes of shoulder pain. Conservative treatment options include physical therapy, pharmacological therapy, and biological therapy. Patients with glenohumeral OA present shoulder pain and decreased shoulder range of motion (ROM). Abnormal scapular motion is also seen in patients as adaptation to the restricted glenohumeral motion. Physical therapy is performed to (1) decrease pain, (2) increase shoulder ROM, and (3) protect the glenohumeral joint. To decrease pain, it should be assessed whether the pain appears at rest or during shoulder motion. Physical therapy may be effective for motion pain rather than rest pain. To increase shoulder ROM, the soft tissues responsible for the ROM loss need to be identified and targeted for intervention. To protect the glenohumeral joint, rotator cuff strengthening exercises are recommended. Administration of pharmacological agents is the major part next to physical therapy in the conservative treatment. The main aim of pharmacological treatment is the reduction of pain and diminution of inflammation in the joint. To achieve this aim, non-steroidal anti-inflammatory drugs are recommended as first-line therapy. Additionally, the supplementation of oral vitamin C and vitamin D can help to slow down cartilage degeneration. Depending on the individual comorbidities and contraindications, sufficient medication with good pain reduction is thus possible for each patient. This interrupts the chronic inflammatory state in the joint and, in turn, enables pain-free physical therapy. Biologics such as platelet-rich plasma, bone marrow aspirate concentrate, and mesenchymal stem cells have gathered increased attention. Good clinical outcomes have been reported, but we need to be aware that these options are helpful in decreasing shoulder pain but neither stopping the progression nor improving OA. Further evidence of biologics needs to be obtained to determine their effectiveness. In athletes, a combined approach of activity modification and physical therapy can be effective. Oral medications can provide patients with transient pain relief. Intra-articular corticosteroid injection, which provides longer-term effects, must be used cautiously in athletes. There is mixed evidence for the efficacy of hyaluronic acid injections. There is still limited evidence regarding the use of biologics.

A cell-based screen for inhibitors of flagella-driven motility in Chlamydomonas reveals a novel modulator of ciliary length and retrograde actin flow.

Cilia are motile and sensory organelles with critical roles in physiology. Ciliary defects can cause numerous human disease symptoms including polycystic kidneys, hydrocephalus, and retinal degeneration. Despite the importance of these organelles, their assembly and function is not fully understood. The unicellular green alga Chlamydomonas reinhardtii has many advantages as a model system for studies of ciliary assembly and function. Here we describe our initial efforts to build a chemical-biology toolkit to augment the genetic tools available for studying cilia in this organism, with the goal of being able to reversibly perturb ciliary function on a rapid time-scale compared to that available with traditional genetic methods. We screened a set of 5520 compounds from which we identified four candidate compounds with reproducible effects on flagella at nontoxic doses. Three of these compounds resulted in flagellar paralysis and one induced flagellar shortening in a reversible and dose-dependent fashion, accompanied by a reduction in the speed of intraflagellar transport. This latter compound also reduced the length of cilia in mammalian cells, hence we named the compound "ciliabrevin" due to its ability to shorten cilia. This compound also robustly and reversibly inhibited microtubule movement and retrograde actin flow in Drosophila S2 cells. Ciliabrevin may prove especially useful for the study of retrograde actin flow at the leading edge of cells, as it slows the retrograde flow in a tunable dose-dependent fashion until flow completely stops at high concentrations, and these effects are quickly reversed upon washout of the drug.

A novel stereotaxic approach to the hypothalamus for the use of push-pull perfusion cannula in Holstein calves.

To determine secretory patterns of growth hormone-releasing hormone (GHRH) and somatostatin (SS) and their roles in the regulation of growth hormone (GH) secretion, a method for collecting hypothalamic perfusates, a push-pull perfusion method was developed in calves. With the use of the stereotaxic apparatus for cattle, a cannula was implanted into the hypothalamus of four male calves based upon cerebral ventriculography. Push-pull perfusates were collected at 10 min intervals for 6h and GHRH and SS concentrations in perfusates and plasma GH concentration were determined by EIAs and RIA, respectively. A cannula was implanted into the hypothalamus based on the image of the third ventricle and maintained for 1 month. GHRH and SS showed pulsatile secretion and the pulses for GHRH and SS were irregular in conscious animals. Neither GHRH nor SS secretion had a clear relationship with GH secretion. In the present study, we thus (1) established a stereotaxic technique for approaching the hypothalamus using cerebral ventriculography for calves, and (2) demonstrated that GHRH and SS secretion were pulsatile but not closely related to GH profile in conscious calves. The technique is useful for the study of the functions of the hypothalamus in the control of pituitary hormones in cattle.